Cytoplasmic Membrane Systems

 

The ................................................ is Comprised of the Endoplasmic Reticulum, Golgi Apparatus, Endosomes, Lysosomes, and Vacuoles

 

Other Membrane Organelles Such as the Mitochondria, Plastids (Chloroplasts etc) and Peroxisomes are ......................................... Endomembrane System

 

The Endomembrane Sytem is a Dynamic, Integrated Network in Which ................................................................... from One Part of the Cell to Another

 

Materials Move Around the Endomembrane System in Numerous Small "Bubbles" of Membrane Called .......................... that Bud off From a Donor Membrane Compartment

 

Vesicles Such as Transport Vesicles Move Through the Cytoplasm in a Directed Manner, Pulled Along the ................................................... of the Cytoskeleton by Motor Proteins

 

When the Vesicle gets to its Destination its ................................................. are Absorbed into the Receiving Membrane Compartment

 

Cycles of Vesicle Budding and Fusion Move Materials Around the ............................................................

 

Several Pathways of .......................................... (Vesicles) Through the Cell have Been Determined

 

A .............................................. Exists, where Proteins are Synthesized in the Endoplasmic Reticulum, Modified During Passage Through the Golgi Complex

 

Proteins are .................................................... to Various Destinations Such as the Plasma Membrane, Lysosomes or Vacuoles in Plant Cells

 

This Route is Also Referred to as the ..........................................,  as Many Proteins and Complex Polysaccharides Synthesized are Destined to be Secreted

 

.................................................. of the Cell Can be Divided into 2 Types

 

.................................................. where Materials are Made, Transported and Secreted in a Continuous Fashion

 

Most Cells Engage in ................................................... to Form and Maintain the ECM and Plasma Membrane

 

In Regulated Secretion, Materials are Stored in Membrane-Bound packages and Secreted in ............................................................

 

Some Examples of ................................................would be Endocrine Cells that Release Hormones, Pancreatic Ascinar Cells that Release Digestive Enzymes and Nerve Cells that Release Neurotransmitters

 

In Some Cells, Materials to be Released are Stored in Large Membrane Bound ...............................................

 

While Materials Move Out of the Cell by the Secretory Pathway, the .................................... Operates in the Opposite Direction

 

In the ........................................., Materials Move From the Outer Surfaces of the Cell to Cell Compartments, Such as Endosomes and Lysosomes Within the Cytoplasm  

 

Just Like with a Transport Company Like Fed Ex, Materials in the Cell have to be ................................................ and Delivered to the Right Destination

 

In ........................................., Mucus Made in the Endoplasmic Reticulum (ER) has to be Targeted to Secretory Granules, Whereas, Lysosomal Enzymes Made in the ER have to be Targeted to Lysosomes

 

Different Organelles Also Contain Different Integral Membrane Proteins and these Also Have to be ............................................................. After Synthesis

 

Secreted Proteins, Lysosomal Enzymes and Membrane Proteins are Routed to the Appropriate Destination by ............................................

 

The .......................................... are Recognized by Specific Receptors that Reside in the Membranes of Budding Vesicles

 

These Receptors Ensure that Proteins are Transported to the .............................................

 

Techniques Used to Study Endomembranes

 

Radioactively Labeled Amino Acids can be Used to Follow the Progress of Proteins Through the .........................................................................

 

A Pulse of Radio-Labeled Amino Acids is Given to Cells and this is 'Chased' by .........................................................................

 

The Radioactive Amino Acids are Incorporated into Proteins and their Progress Through the Endomembrane System is Monitored ..........................................................

 

More Recently, Proteins can have Part of the ........................................................ (GFP) from Jellyfish Tagged onto the End of the Coding Region of Their Genes

 

This Makes Proteins .......................................... Under a Fluorescence Microscope; Progress of the Proteins Through the Endomembrane System can Then be Studied

 

We can Also Homogenize Cells and Isolate Different Parts of the Endomembrane System .........................................................................................................

 

Here Large Particles Like Organelles Spin Down at Low G-Forces in ..................................

 

Increasingly Smaller Particles Like ....................................Spin Down at Higher G-Forces

 

Different Types of Microsomes can be Separated Using a ........................................., where Microsomes of Different Densities Congregate at their Respective Densities in the Gradient

 

The Molecular Components Present in Each Microsome Fraction can then be Determined by ...................................

 

Other Techniques Such as Proteomics/ ..................................................... Can be Used in Genome-Sequenced Organisms Such as Humans

 

This Can Determine the Identity of Each Component from a ................................................. of its Molecular Weight

 

Researchers have Also ...................................................................... to Study the Function of the ER and Vesicles

 

The Figure Shows Artificial Liposomes With Added Coat Proteins in the Process of Budding Off ............................................

 

Genetic Mutant in Genes Involved with Endomembranes Can Easily be ...............................

 

This is Because Yeast:-

                                                1) has Relatively Few Genes in its ...................,

                                                2) they are Singled Cell Organisms which are Easy to ........................

3) they are Haploid, so Every Mutation in the Coding Region of a Gene will have an ............................

 

Yeast Cells are Randomly Mutated by DNA- Interfering .......................................................

 

Any Cells with Abnormalities in Endomembrane Function are ............................................

 

All the Genes whose Proteins are ................................................... have Therefore Been Determined

 

As Most Yeast Proteins have Recognizably ................................................... in Other Species Such as Humans, they can be Further Studied there

 

This is Because Proteins Involved in Endomembrane Function are .......................................

 

Consequently, Human Endomembrane Protein Genes can .................................. for Yeast Genes or Vice Versa and they Still Function Correctly

 

The Endoplasmic Reticulum

 

The ER is Divided into 2 Sub-Compartments the .............................................................. that do Different Jobs

 

The Composition of the Luminal or Cisternal Space Inside the ER is ...............................................

 

Proteins and Lipids Can Diffuse Between the RER and SER, Showing that their Membranes are .............................................

 

The RER and SER Share Some Activities Such as Synthesis of Some ................................................................

 

However, Certain Proteins are Only Found in the .................................

 

The Main Structural Difference is that the RER has .................................Attached to it, which the SER Does Not

 

The RER is Composed of layers of Interconnected Flattened Sacs ...................... (Like Connected Pitta Breads)

 

The RER is Continuous (Connected to) with the Double Membrane Surrounding the Nucleus (Nuclear Envelope) which Also has ......................................

 

By Contrast, the SER is a Network of Interconnected ..........................(Tubes)

 

Different Types of Cells Contain Markedly Different Amounts of the 2 Types of ER Depending on the ....................................

 

Cell Types that ........................... Proteins as in the Pancreas or Salivery Glands have lots of RER

 

Cells Types that Produce ..................................... (Gonad and Adrenal Cortex) or Detoxify Organic Compounds (Liver) have lots of SER

 

The Endoplasmic Reticulum:-SER

 

The ................................................. in Cells Within Skeletal Muscle, Kidney Tubules, and Steroid-Producing Endocrine Glands (Gonad and Adrenal)

 

In Liver, the SER Detoxifies Barbiturates, Ethanol and Other Organic Compounds, Using .......................................................... Oxygenase/Oxygen Transferring Enzymes

 

The Continued or the Elevated presence of these Compounds in the Bloodstream Leads to ............................................................ in Liver Cells

 

The Function of Detoxifying Enzymes in Liver SER is to Add ....................................... to Compounds to make them More Soluble so they Can be Excreted in the Urine

 

Cytochrome P450's Actions Can be Deleterious as the Compound Benzo [a] Pyrene, Produced when Food is Burnt, is Turned into ..........................................

 

Other Drugs and Medicines are Also Metabolized and Genetic Differences May Explain Differences in the Side Effects ............................................

 

.................................... in Liver Cells is Stored in Granules Near the SER

 

When Energy is Needed the Hormone ........................... is Released by the Pancreas

 

Glucagon Stimulates the Breakdown of Liver Glycogen Stores to ............................ which is Converted by the Glucose-6-Phosphatase Enzyme in the SER Membrane to Glucose, which is Released into the Bloodstream

 

The SER is Also Involved in Sequestering .................................., Particularly in Skeletal and Cardiac Muscle Cells

 

Uptake of Calcium into the SER via the ..................................................... And Also by Other Organelles and the Plasma Membrane, Keeps Intracellular Calcium Concentrations Really Low

 

The Regulated Release of Calcium from the SER Through ......................................, Acts as a Second Messenger and Triggers Muscle Contraction

 

The Endoplasmic Reticulum:-RER

 

The Function of the Rough ER was Originally Studied in ................................

 

The ....................at the bottom of the Cell Begins the Biosynthetic Pathway by Making Proteins Carbohydrates and Phospholipids

 

These Products Move Up the Cell to the ..................................... and then into Secretory Granules, from which they are Subsequently Secreted

 

The Secretory Cell Shows One Type of Protein Made by Ribosomes Attached to the RER, ......................................................

 

RER Ribosomes Also Make:-

                        1) .................................................... Proteins

                        2) Proteins that ................................................... Within the Endomembrane System

 

Other Proteins are Made in the Cytosol on 'Free' Ribosomes and these Include:-

                        1) ........................... Proteins,

                        2) Peripheral Proteins Attached to the Inside of the .......................................,

                        3) Proteins that are Transported to the .................................

                        4) ..................... Incorporated into Mitochondria, Plastids and Peroxisomes

 

Secretory Proteins Made in the ER ................................................ at the N-terminal that Directs the Emerging Polypeptide and Ribosome to the ER Membrane.

 

The Concept of Signal Peptides as Part of Proteins is Known as the .....................................

 

The Polypeptide Moves into the Lumen of the ER Through a Protein-Lined .........................................................in the ER Membrane

 

The Polypeptide Essentially Moves through the Membrane as it is .......................................

 

The Endoplasmic Reticulum:-RER Protein Synthesis

 

The Synthesis of a Protein Begins with Binding of a .................................... to a mRNA Encoding the Protein, in the Cytoplasm

 

Secretory, Lysosomal, or Plant Vacuolar Proteins Contains a 6-15 Amino Acid Hydrophobic ............................................ that Targets the Nascent Polypeptide to the ER Membrane and Leads to Compartmentalization of the Polypeptide in the ER Lumen

 

As the Polypeptide is Made by the Ribosome, the Signal Sequence is Recognized by a ...................................................................... (SRP)

 

The ............. Consists of 6 Separate Polypeptide + 1 RNA Molecule Called the 7S RNA

 

The SRP Binds to Both the Signal Sequence of the Polypeptide and ................................

 

Further Polypeptide Synthesis is ...........................Until the SRP/Polypeptide/Ribosome Complex Docks and Attaches Specifically to the RER Membrane

 

So the Interaction Between the SRP and the Signal Sequence Determines Whether the Protein will End Up ...............................................................................

 

Binding of the Complex to the ER membrane Takes Place in ........................

 

The SRP Binds to .............................................. in the ER Membrane and then the Ribosome Binds to the Translocon in the ER Membrane

 

The ............................is the Protein-Lined Pore Through which the Polypeptide will Travel to Arrive Inside the ER Lumen

 

Once the .............................................. to the Translocon, the SRP is Released from its Receptor and the Polypeptide is Inserted into the Aqueous Pore of the Translocon

 

Translation of the mRNA by the Ribosome ..................................... and the Polypeptide is Translocated Through the Translocon into the ER Lumen

 

After Translation Finishes, and the Polypeptide has Moved Through the Translocon, the .................................................

 

Several Steps in the Synthesis and Trafficking of Secretory Proteins etc, Involve Regulation by .................................... (GTP-Binding Proteins that Hydrolyze GTP)

 

G-Proteins have ..........................................., Generally they are On when GTP is Bound and Switched Off when that is Hydrolized to GDP

 

The SRP and its Receptor are ........................................

 

Hydrolysis of the GTP Attached to the SRP Causes the Release of the .............................................................. and its Insertion into the Translocon

 

When the Polypeptide Enters the Lumen of the ER the Signal Sequence is Removed by a Proteolytic Enzyme Called a .................................................

 

........................................are Added to the Protein by the Enzyme Oligosaccharyltransferase

 

Both of these Enzymes are ...................................... Proteins, Situated Near the Translocon in the RER

 

The RER Lumen Contains ................................................... Such as BiP or Calnexin, that Recognize and Bind to Unfolded or Misfolded Proteins, and Give them the Chance to Reorganize into the Correct Structure

 

The ER-Lumen Also Contains the Enzyme, ............................................................, which Forms and Reshuffles Disulfide Bonds Between Cysteine Amino Acids in Proteins

 

Disulfide Bonds Play a Major Role in Stabilizing Proteins on the Extracellular Surface of the Plasma Membrane or those that are ................................................................

 

The ER is the Ideal Place to Begin the Biosynthetic Pathway Due to its ................................ to Attach Ribosomes to

 

The ER Lumen Provides an Idea Environment for the .................................... of Secretory, Lysosomal and Plant Vacuolar Proteins, which are Segregated Away Other Synthesized Proteins

 

This ....................................is the First Part of the Sorting, that Allows the Proteins to be Modified and then Delivered to their Ultimate Destination

 

Integral Membrane Proteins, Other than those of Mitochondria, Plastids or Peroxizomes, are Also Synthesized ...............................

 

The Membrane Proteins are Also Translocated into the RER ...................................... (ie Cotranslationally)

 

However, Integral Proteins Contain One or More Transmembrane Segments that ......................................................................into the ER Lumen

 

The Transmembrane Segments, Called Stop-Transfer Sequences, Include a Run of Around 15 Hydrophobic or Uncharged Amino Acid Residues that Allow .............................. into the ER Membrane

 

Once the Segment is Released from the Aqueous Channel of the Translocon, It is ............................................. into the Membrane of the ER

 

It is Unclear Whether the Transmembrane Segments Leave the Translocon One or Two at a Time or ............................................................. has Been Completed

 

Single membrane Spanning proteins Can be Inserted ...................................... in the ER Membrane

 

The Orientation is Determined by ................................................................. Near the Membrane Span on One Side of the Membrane

 

The Cell Inserts the Membrane Span with the More Positive Side Facing the ...................

 

In Multispanning Transmembrane Proteins, Sequential Membrane Spans Have ..................................................... (ie the Polypeptide Chain Goes Across the Membrane and then Back Across to the Original Side Again)

 

So During Synthesis, Every Other Alternate Membrane Span has to be ............................. Before it Leaves the Translocon

 

The ............................... is Therefore a Complex Mechanism Capable of Recognizing Signal Sequences and of Performing Complex Mechanical Maneuvers

 

The Endoplasmic Reticulum:-Membrane Lipid Biosynthesis

 

New Membrane Only Arise from ........................................, as newly Synthesized Lipids are Inserted into the Membranes of the ER

 

Membranes from the ER then Move to Most Other ......................................... of the Cell

 

As Membranes Move from One Compartment to the Next, Their Proteins and Lipids are ............................... Giving Each Compartment a Unique Membrane Composition

 

The ......................... of the Lipid Bilayer is Initiated in the ER

 

Proteins and Lipids are Preferentially Placed into .......................................

 

The Asymmetry Produced is ..........................as Vesicles Bud and Fuse with Successive Membrane Compartments

 

Consequently, Components on the ............................... of the ER can Also be Found on the Cytosolic Faces of Vesicles, Golgi Cisternae, and the Plasma Membrane

 

Similarly, Components Found on the ................................... of the ER Membrane Maintain their Orientation

 

They are for Example, Found on the External Surface of .......................................

 

The Environment Inside the ER Lumen is a Lot Like the .......................................

 

It has a High Calcium Concentration, Oxidizing Potential, and ..............................

 

Most Membrane Lipids are Synthesized Entirely Within the ................

 

The Exceptions are:-

 

1) ................................................................. whose Synthesis Begins in the ER but is Completed in the Golgi Complex

 

2) Some Unique Mitochondrial and Plastid Lipids that are ........................................ Residing in their Own Membranes

 

ER Phospholipid Synthesizing Enzymes are Integral Membrane Proteins whose Active Sites .....................................

 

Newly Synthesized Phospholipids are Inserted into the Side of the Bilayer Facing the ....................

 

Some of the Lipids are Later ............................................. of the Bilayer by Flippases

 

ER Lipids are Carried to the .................................... in the Walls (Membranes) of Transport Vesicles

 

The Membranes of Different Organelles have Markedly .............................................

 

The Different Organelle Lipid Compositions Indicate Changes Occur ...................................................... from One Compartment to Another

 

This is Due of Several Factors:-

 

Most Organelles Contain Enzymes that ...........................

 

Certain Lipids Can be Selectively ................................................ from Vesicles

 

Cells Contain Phospholipid Transfer Proteins that can Transfer Lipids Through the Cytosol from ........................................................................

 

The Phospholipid Transfer Proteins are Especially Important for Delivering Lipids to .......................................................................................

 

These Organelles Do Not ................................................... and are Not Part of the Endomembrane System

 

Consequently, these Organelles DonÕt Obtain Lipids Through the .............................................................

 

The Endoplasmic Reticulum:- Protein Glycosylation

 

Nearly All Proteins Produced by the RER Become ................................

 

The Attached Carbohydrate Groups Play Key Roles in the Function of ......................, Especially as Binding Sites for Other Macromolecules

 

......................................... Also Aid in the Proper Folding of the Protein to which they are Attached

 

The .............................................. in Each GlycoproteinÕs Oligosaccharides is Highly Specific, Consistent and Predictable

 

The Addition of Sugars to an Oligosaccharide Chain is Catalyzed by Membrane Bound Enzymes ..............................................................

 

............................................ Transfer a Specific Sugar Monosaccharide from a Donor to an Appropriate Sugar Acceptor

 

The Donor is Always a ....................................., Such as CMP- Sialic Acid, GDP-Mannose or UDP-N-Acetylglucosamine

 

The Acceptor Molecule that Receives the Sugar is the Growing End of the ................................................

 

The Sequence of Sugars Added to the Chain Depends on the Sequence of Action of the ................................................................ Involved

 

The Order in which Glycosyltransferase Participate in Adding Sugars, Depends on the Location of the Specific Enzymes within the Membranes of the ...............................

 

So the Arrangement of Sugars on Glycoproteins Depends on the Spatial Distribution of ........................................................ within the Endomembrane System

 

With .................................................. (as Opposed to O-Linked), the core Segment of Carbohydrate Chain is Not Assembled on the Protein

 

Instead it is Put Together Independently on a Lipid Carrier, and then Transferred to Specific ............................................ of the Protein

 

The Lipid Carrier, ........................................, is Embedded in the ER Membrane

 

Sugars are Added to the ...................................... One at a Time by Different Glycosyltransferases

 

Part of the Glycosylation is Invariant in .....................................

 

It Starts with Sequential Addition of:-

                        1 N-aceylglucosamine 1-phosphate,

                        1 N-aceylglucosamine,

                        9 Mannose Sugars,

                        3 Glucoses

 

The Pattern of ................................. is Indicated in the Diagram

 

The Block of 14 Sugars Formed, is then Transferred by the ER Enzyme ....................................................

 

It is Moved from the Dolichol Phosphate to ............................... Residues on the Protein

 

Mutations that Lead to the Loss of ..................................... Lead to the Death of Embryos Prior to Implantation

 

Partial Disruption of N-glycosylation is Responsible for .............................................

 

These Diseases are Called ......................................................................... (CDGs)

 

The Disorder CDG1b is a Deficiency in the Enzyme ................................... which Makes Mannose-6 Phosphate from Fructose-6-Phosphate

 

This can be Easily Treated with a Dietary Supplement of .....................

 

................................. in Lower Eukaryotes is Essentially the Same as Shown

 

The Evolution of Higher Eukaryotes Led to Diversification of ....................................... Attached to Proteins

 

Modification of Core Oligosaccharides in the ER Begins with Removal of 2 of the Terminal ......................................

 

Each Glycoprotein with a Single Glucose Binds to an ................................... (Calnexin or Calreticulin)

 

This Gives the Protein the Opportunity to ...................................

 

The Remaining Glucose is Removed and the Glycoprotein is Released from the ...................................

 

If the Protein is Not Properly Folded it is Monitored by the Monitoring Enzyme, GT, which Adds back a ..................................... to the Terminal Mannose

 

GT Recognizes Misfolded Proteins Because they Display Exposed ..........................Residues

 

Once the Glucose is Added by GT the Protein can Bind Again to the ......................... and Attempt to Fold Correctly Again

 

This Process is Repeated Until the Protein is Either .............................. and Proceeds Through the Endomembrane System

 

Or the Protein Remains Misfolded and ................................

 

............................................. Begin their Journey to Degradation by a Process of Reverse Translocation

 

They Pass Back Through the ................................................., where any Oligosaccharides are Removed

 

The Proteins are then Degraded in ..............................

 

The Process of Degradation of Misfolded Proteins is a Form of .................................

 

It Ensures the ........................................ are Not Transported to Other Parts of the Cell

 

Mutations of the ................................... Gene Produce Proteins Which Function Correctly as Ion Channels

 

However, these Channels Never Reach The Plasma Membrane as they are Somewhat Misfolded and so are .......................

 

Under Certain Circumstances ................................... can be Made at a Faster Rate than they can be Exported Back to the Cytoplasm

 

This Triggers a Response Known as ..........................................................

 

The ER Contains Proteins that ............................................. of Unfolded Proteins Present in the ER Lumen

 

These Sensor Proteins are Kept Inactive by the ....................................................

 

If the Amount of Unfolded Proteins in the ER Increases, the ........................... are Needed to Try and Refold these Proteins

 

So they Detach from the Sensors to do this Job Allowing the ...........................................

 

....................................... Leads to a Range of Signals that are Transmitted to Both the Cytoplasm and Nucleus

 

The ...................... from the ER Sensor Proteins Result in:

 

The Expression of Hundreds of Genes whose Proteins will ................................ in the ER, Including:

 

                        1) Extra ER .................... Proteins

                        2) Extra Proteins that .................................... Proteins Out of the ER

                        3) Proteins Involved in the ................................................... Proteins

 

A Key Protein for Initiation of Protein Synthesis is Also ..................................to Prevent Initiation and Reduce Synthesis

 

The Inhibition of Protein Synthesis Gives the Cell the Opportunity to ........................... of Misfolded Proteins Out of the ER

 

The ................................................ is More than a Mechanism to allow to Survive a Problem with Excess Misfolded Proteins

 

The Unfolded Protein Response Also Activates the ........................................... Pathway

 

If the Measures to Correct the Level of Misfolded Proteins Present are ......................., the Cell will Die

 

From the ER to the Golgi

 

The Movement of Materials from the ER to the Golgi can be Followed by .................. Molecules

 

As Transport Vesicles Leave the ER they Form Larger Vesicles and Interconnected Tubules in the Region Between the ....................................

 

This Region is Known as the ER-Golgi Intermediate Compartment or ..................

 

The Vesicular-Tubular Clusters that Form in the ERGIC are ..........................

 

Once the VTCs have Been Formed they Move Away from the ..............................

 

The Movement of the VTCs is Along .............................

 

The Golgi Complex

 

The Golgi has a Structure of Flattened Cisternae that Exist as a .................................

 

Each Golgi Cisternae is Around 0.5-1 um Thick and There Usually ............................. in the Stack

 

However, a Cell may Contain from a Few to ............................................., Depending on Cell Type

 

The Golgi Stacks in Mammalian Cells are Interconnected by ................................... to Form a Ribbon Like Complex Near the Cell Nucleus

 

Vesicles Bud from the ............................................... of Each Cisternae

 

The Golgi Complex is Arranged into Several ........................................... Compartments from the Cis- to the Trans-Face

 

The Cis-Face is the ............................... and is Closest to the ER, and the Trans-Face is the Exiting Face at the Opposite End of the Stack

 

The Cis-Face is Comprised of a Network of Interconnected Tubules Known as ........................................... (CGN) and Receives the VTCs

 

The CGN is a Sorting Center Which Sorts Proteins to be ........................................ from those that will Continue Through the Golgi

 

The Golgi Complex Cisternae are Divided into .....................................Cisternae

 

The Trans-Face is Also a Network of Tubules and Vesicles Called ...................................................... (TGN)

 

The TGN Also Sorts Vesicles Going to the Plasma Membrane or to .................................................

 

The Membranes of the Golgi Complex are Supported by a Skeleton or Scaffold of Proteins, Including .......................................................... Isoforms

 

The Golgi Scaffold is Linked to ................................ that Direct the Movement of Vesicles and Tubules Entering and Exiting the Golgi Complex

 

A Separate Group of Fibrous Proteins Form a Golgi Matrix that Plays a Role in Disassembly and Reassembly of the Golgi During ...................

 

The Golgi is a ..................................... with Different Functions in Different Cisternae

 

Proteins and Protein-Linked Carbohydrates are ......................................................., in a Stepwise Fashion, by Enzymes, as they Pass Through the Various Golgi Compartments

 

The Golgi Complex; Glycosylation

 

When Glycoproteins Arrive in the Golgi, After Having Terminal Glucoses Removed in the ER, Most of the ............................... are Also Removed in the Golgi

 

The Mannose Sugars are Replaced by Other Sugar Groups Added Sequentially by Various ..........................................

 

The Sequence of Added Sugars is Again Determined by ..................... that the Glycoproteins Meet the Particular Glycosyltransferase Enzymes

 

The Enzyme ............................... that Adds Salic Acid Monomers to the Terminal Ends of the Oligosaccharides is Located in the Trans Golgi

 

However, Unlike in the ER, the Glycosylation Events in the Golgi can be ......................... Producing a Diversity of Glycosylation of Proteins

 

In Addition to N-linked Glycosylation, ....................................... Also Occurs in the Golgi

 

The Golgi is the Site of Synthesis of Most of the CellÕs ....................................., Including Glycosaminoglycans and, Pectins and Hemicelluloses of Plant Cell Walls

 

The Golgi Complex; Movement of Materials

 

There are 2 Models which Seek to Explain How the ............................

 

The First Model is the ................................................

 

Here the Cisternae Mature and ............................. the Trans Face of the Stack as they Go

 

Retrograde Vesicles Shuttle Back and .............................. Already Used in One Cisternae Back to the Next One

 

This ..........................................., Enzymes Found in the Cis Golgi, in that Location

 

This Model is Based on the Fact that there are Proteins in the Golgi Lumen, Such as ..................................,  that Never Appear in Vesicles

 

The Second Model, ........................................... is where Vesicles Move in a Anterograde Fashion

 

They Move ................................... from the Cis End of the Stack to Subsequent Cisternae

 

The Cisternae Themselves are However ................................... that do Not Move

 

So the Enzymes in the Cis Golgi ........................................... and Only Products, Proteins and Carbohydrates Need to Move in Vesicles

 

Both Models have Problems as they ................................. with the Available Information

 

There Does Appear to be Both .................................................. Vesicles Moving Between Cisternae

 

Some Vesicles Contain ....................................

 

Some Products Like Procollagen ...................................... Vesicles at All

 

It Seems the Answer is a Model that .....................................................

 

The Golgi Complex; The Role of Vesicles

 

As Already Mentioned Material is Carried Between Endomembrane Compartments by .......................................................

 

Vesicles are ...................................... and Bud from One Membrane Compartment and Fuse with the Next

 

Most Vesicles have a .............................................. that Forms from Soluble Proteins

 

The Coat Proteins Assemble on the Surface of the Membrane where ..............................................................................

 

Each Vesicle Bud, Buds Off to Form a ...................................

 

The Protein Coats have 2 Functions:

 

                        1) They Act as a Mechanical Device that Causes ....................................... and promotes Budding

                        2) They Provide a Mechanism to ............................................ Being Transported

 

Selected Components Include,

 

                        1) The ............................................. or Membrane Proteins to be Transported

                        2) The ........................................................... the Vesicle to the Correct Membrane Compartment

 

Protein Coats are able to Make the Selections Based on the ............................................... Proteins that Reside in the Donor Membrane

 

Several Distinct Classes of Coat Protein Exist that ...........................

 

1....................................... Move Materials Forward From the ER to the ERGIC and Golgi Complex

 

2) .................................................. Move Materials Backwards From Golgi Stacks and the ERGIC towards the ER

 

3.................................................. Move Material From the TGN to Endosomes, Lysosomes and Plant Vacuoles

 

Clathrin-Coated Vesicles Also Move materials from the Plasma Membrane to Cytosolic Compartments Along the ......................................

 

Clathrin-Coated Vesicles are Also Involved in Trafficking Materials from ...................................................

 

The Golgi Complex; COPII-Coated Vesicles

 

COPII-Coated Vesicles are Involved in the First Step of the Journey Materials Take After the ER, to the ..................................

 

The COPII Coat Contains .................................. Initially Identified in Mutant Yeast Cells

 

Antibodies Against mammalian COPII Protein Homologues .............................................. Vesicles from the ER, but have No Effect on Other Stages of Transport

 

COPII Coats Select for and ................................... Components for Transport in Vesicles

 

Certain ER Integral Proteins are Concentrated Because they Contain an ........................ as Part of their Cytosolic Tails

 

These Signals Specifically Interact with .............................................

 

The Proteins Selected Include

 

1) Enzymes that Function .........................................................., Like Glycosyltransferases

2) Membrane Proteins Involved in ................................................

3) Membrane Proteins that are Able to ...........................................

 

Mutations in these ................................ have Been Linked to Bleeding Disorders

 

One of the COPII Coat Proteins is a ........................................., which Regulates the Assembly and Disassembly of the Vesicle Coat

 

Upon Binding GTP, ........................................... and Causes itÕs N-Terminal a-Helix to Attach to the Outer Leaflet of the ER Bilayer

 

The Presence of Sar1 in the Membrane Primes that Site and Allows ....................................................... to Form a Coated Vesicle Bud

 

Before the Vesicle Formed Can Fuse with a Target Membrane, the Protein Coat Must be ................................and the Coat Components Released into the Cytosol

 

Disassembly is Triggered by .................................................., which Returns  Sar1Õs Conformation Back to the Original One and Reduces itÕs Affinty for the Membrane

 

Dissociation of Sar1 from the Membrane ..........................................................

 

The Golgi Complex; COPI-Coated Vesicles

 

In a Similar Fashion to COPII Vesicles, COPI Vesicles Contain a ......................................................., whose Bound GTP has to be Hydrolyzed to Disassemble the Coat

 

COP1 Vesicles Mediate the ................................. of Materials Between Compartments

 

........................................... have Been Implicated in the Movement of:

 

                        1) ..............................................., Moved from Trans to Cis Cisternae

 

                        2) ...................................... Returned from the Golgi and ERGIC to the ER

 

Proteins and Enzymes Present in a Particular Compartment are Maintained in that Location by ..............................

 

1) Resident Molecules in a Compartment are ...............................................................

 

2) Any Molecules Still Escaping the Compartment are ............................. to where they Normally Reside

 

ER Resident Proteins have a ...................................... Sequence at their C-Terminus that Acts as a Retrieval Signal

 

So Any ER Proteins Reaching the ERGIC or Cis Golgi are .............................

 

This is Achieved by Recognition of the Signal Sequence and Capture of that Protein by a ..................................

 

These Proteins/Receptors are then Included in ............................ and Returned to the ER

 

Soluble ER Luminal Proteins Like Protein Disulfide Isomerase and Chaperones have the Retrieval Signal ....................................................

 

Soluble ER Proteins in the ERGIC and Golgi Bind the ........................... and are Returned to the ER

 

The ........................................ Shuttles Back and Forth Between these Compartments

 

If the KDEL Sequence is Deleted from an ER Protein, it ................................................. the Golgi Complex

 

If a Secretory or Lysosomal Protein has the KDEL Sequence Added, it is ..................... to the ER

 

Resident Membrane Proteins of the ER, Such as the ................................ have a Slightly Different Retrieval Signal, KKXX at their C-Terminus; where X is Any Amino Acid

 

The ............................................ to the COPI Coat Facilitating the ProteinÕs Retrieval

 

Each Membrane Compartment in the Biosynthetic Pathway has its Own ....................... which is Why they Each have Distinct Sets of Different Enzymes

 

The Golgi Complex; The TGN

 

The TGN is the Major Processing Center where Proteins Destined for Different Sites are ............................................. Membrane-Bound Carriers

 

The Best Understood Post-Golgi Pathway Involves ...........................................

 

.................................... are Synthesized on Ribosomes in the ER and Carried to the Golgi

 

In the Golgi, the Enzymes are Recognized by Enzymes that Catalyze the 2-Step Addition of a .................................. to Certain Mannose Residues that Act as a Recognition Signal

 

Lysosomal Enzymes Carrying this Mannose-6-Phosphate Signal are Recognized and Captured by .........................................................., that are Integral Membrane Proteins of the TGN

 

Lysosomal Enzymes are Transported from the TGN in .................................................

 

Clathrin Coated Vesicles have a Honeycomb-Like Lattice of the Protein, ......................

 

Clathrin Forms a Scaffold for an Inner Shell of ................................. that Cover the Surface of the Vesicle that Faces the Cytosol

 

Lysosomal Enzymes are Escorted from the TGN by a Family of Adaptor Proteins Called ...................

 

GGA Proteins have .................................. Each One Binding to a Different Protein On the Vesicle

 

One of the Domains Binds ........................, Holding ItÕs Scaffold onto the Surface of the Vesicles

 

The GGA Also Binds to the Sorting Signal in the Cytoplasmic Tail of the ..............................................................

 

The Mannose-6-Phosphate Receptors are in Turn Bound to Soluble .................................. in the Vesicle Lumen

 

As a Result of these Interactions the Lysosomal Enzymes Become ..................................................... in the TGN

 

As with COPI and COPII Vesicles, the .............................. Effectively Allows the Binding of Coat Proteins at the Site where ARF1 is Itself Bound to the Membrane

 

Once the Vesicle Buds from the TGN, the Clathrin Coat is ....................................... Again

 

The .................................. is then Moved to its Destination

 

But Before the Vesicle Reaches Its Destination, the .................................................... Release the Bound Soluble Enzymes and Return to the TGN

 

Proteins are Also Exported from the TGN to .....................................

 

Secretory and Membrane Proteins Destined for the Plasma Membrane Also Leave the TGN in Vesicles ...............................................

 

Here the Proteins Concerned are Thought to ............................. which are then Partitioned into Particular Membrane Bodies as the TGN Fragments into Vesicles/Secretory Granules

 

Secretory Granules in Particular Bud of the Trans-Golgi or TGN and are Stored ......................................................at the Cell for their Release

 

The Delivery of Integral Proteins to the Plasma Membrane Occurs Due to Sorting Signals Present in their .........................................

 

Polarized Epithelial Cells Represent an Additional Challenge as Different Proteins are Sent to the ............................................... Membrane Domains

 

The Sorting Signals for Each Membrane Domain ..................................

 

Apical Proteins Tend to be Found in ................................. that Form in the TGN

 

Plasma Membrane Proteins in ....................................... Do not Need any Kind of Special Sorting Machinery and Can Just be Carried to the Surface in Vesicles of the Constitutive Secretory Pathway

 

The Golgi Complex; Vesicle Targeting

 

....................... Requires Specific Interactions Between the 2 Membranes Concerned

 

Selective Fusion is One Factor that Ensures a .............................. Through the Various Endomembrane Compartments Starting at the ER

 

Vesicles Contain Specific Proteins Associated with the Membrane that Govern the .......................................... of the Vesicle

 

The Identity of .............................. Concerned has Not Yet Been Fully Determined

 

Some Parts of the Process of ............................ have Been Determined Including

 

1) Movement of Vesicles Towards the Target Compartment For Fusion is Mediated by .............................

 

Vesicles are Often Tethered Once they reach the Target Compartment by ...................................................

 

Tethering Requires Compatibility Between the .................................... Compartment

 

The Compatibility is Determined by Members of the .............................. Family

 

Rabs Associate with Membranes by ...............................

 

Over ........................................ have Been Identified in Humans

 

Different .............................. are Associated with Different Membrane Compartments

 

This is what Suggests Rabs have a Role in ....................................................

 

When GTP is Bound to the Rab G-Proteins, they are Thought to Recruit ..........................................to the Membrane Surfaces

 

3) At Some Point ............................... the Membranes Come Close to Each Other

 

This Proximity of the 2 Membranes Results From Integral Proteins ......................... in the 2 Membranes

 

There are Also More than ......................................... Known to Exist

 

Some of these Isoforms Localize to ...................................... Compartments

 

SNAREs Vary in Structure and Size, but All Contain a Segment in their Cytosolic Domain Called .........................................

 

SNARE Motifs Consist of 60-70 Amino Acids Capable of Forming a Coiled Coil with Another ....................................

 

SNAREs are Divided into ..........................

 

......................... which Become Incorporated into the Vesicle During Budding

 

......................... which are Located in the Target Membrane Compartment

 

The Best Studied SNAREs are those Involved in Docking Synaptic Vesicles During ............................ Neurotransmitter Release

 

The Plasma Membrane of the Nerve Cell Contains 2 t-SNAREs, Called ....................................................

 

Whereas, the Synaptic Vesicle Membranes Contain a Single v-SNARE, Called ...................................

 

As the Membranes Approach One Another, the SNARE Motifs of Opposing v- and t-SNAREs form a .......................................

 

Each Bundle Consists of .................................., 2 from Snap-25 and 1 Each from Syntaxin and Synaptobrevin

 

Together these Helices Form the ................................ that Pulls the 2 Membranes into Close Proximity

 

These SNAREs in Nerve Cell Synapses are Targeted by the ............................... Toxins which Act as Protease Enzymes and Cleave Specific Snares in the Synapse, Blocking Neurotransmitter Release

 

Similar .................................. Occur Utilizing Others SNAREs at Other Vesicle Fusion Sites in Cells

 

4) When Artificial Liposomes Containing v- or t-SNAREs are Mixed, the 2 Types of Vesicles Fuse Together, but Not ..........................................

 

This Indicates that the Interaction of the 2 Types of SNAREs is ........................for Vesicle Fusion on their Own

 

Although Interactions Between v- or t-SNAREs is Sufficient in vitro, More is Needed ......................................................

 

The 4 SNAREs in the Bundle in Nerve Cells are Locked in an Inactive Conformation by Another Bound Protein ................................................

 

Vesicles with SNAREs Inactivated ...................................... are Docked at the Membrane Ready to Discharge their Contents Virtually Instantly

 

The Activating Signal which Causes Vesicle Fusion is a ..............................................Ion Concentration

 

Once Membrane Fusion Occurs, the SNAREs Originally in the 2 Membranes Now Occur in the ...............................

 

Dissociation of the 4-Stranded SNARE Bundles is Achieved by a Doughnut-Shaped Cytosolic Protein, ........................, that Attaches to the Bundle and Twists it Apart

 

The Specificity of the Fusion of Vesicles with the Correct Membrane Compartment, is Due to the Specific Combinations ............................................... Present in the Vesicle and the Receiving Compartment

 

In Other Words, Which Particular ..................... of the Tethering Proteins, Rab G-Proteins and SNAREs are Present in the 2 Membranes Involved

 

The Multiple Interactions Between the Several Proteins Involved Allows Enough Specificity for a Vesicle to Fuse Only with the ...........................................................

 

Exocytosis

 

Fusion of a Secretory Vesicle or Granule with the .................................... is Exocytosis

 

Exocytosis Occurs Continually as Proteins and Other Materials are ................................ Plasma Membrane and ECM

 

Some Cells, Such as Nerve Cells, Also have ............................................., in this Case, of Neurotransmitter

 

In these Cases, Fusion Produces an Opening Through Which the Contents of the Vesicle or Granule are ........................................................................

 

In Nerve Cells, the Arrival of the Nerve Impulse at the Terminal Knob, Leads to a Rise in ............................................., Followed by Neurotransmitter Release

 

In Nerve Cells, Vesicle Fusion is Regulated by the Calcium Binding Protein, .........................................Present in the Synaptic Vesicle Membrane

 

In Other Cell Types, Exocytosis is Triggered by Release of ......................from Cytoplasmic Stores

 

Contact Between the Vesicle and the Plasma Membrane Results in a Protein-lined Fusion Pore which Sometimes Recloses but Usually ....................to Allow the Vesicle Contents into the Extracellular Space

 

The Vesicle Membrane then Becomes Part of the ................................... of the Cell

 

Lysosomes

 

Lysosomes are Animal CellÕs ........................Organelles

 

A Typical Lysosome Contains ...................................... Produced in the ER and Shipped to Lysosomes in Vesicles

 

Lysosomal Enzymes can Hydrolyze Virtually Any Type of ..........................................

 

Lysosomal Enzymes All Have an Optimal Activity at an ....................and are thus Acid Hydrolases

 

The Activity Optimum is Suited to that of the Lysosome, which has a ..........................

 

The Internal Lysosomal pH is Maintained by a Membrane-Bound ................................... Pump

 

Lysosomes Contain a Variety of Integral Membrane Glycoproteins with ....................... that Shield the Membrane from Attack by the Enclosed Enzymes

 

Lysosomes Contain a Predictable Collection of Enzyme but ...................................... from 25-50nm to 1um (1000nm)

 

Lysosomes have a Number of .....................................

 

Firstly, they ........................................ Brought into the Cell from the Extracellular Environment

 

Many Single-Celled Organisms Ingest Food Particles which are .................by Lysosomes

 

In Mammals, Phagocytic Cells, Like Macropharges and Neutrophils ..........................................................

 

Ingested Bacteria are Inactivated by the Low pH and are ........................in Lysosomes

 

Peptide Breakdown Products are ........................................................ to Alert the Immune System to the Foreign Agent

 

Lysosomes Play a Role in the Regulated Turnover, Destruction and Replacement, of the ..........................................

 

This Process is Known as ..............................

 

Organelles Like Mitochondria are Initially Surrounded by the Double Membrane of Part of the ER, Forming a .........................................

 

The ER then Fuses with a Lysosome to Form a ...............................................

 

It has Been Calculated that 1 Mitochondria Undergoes .................................. Every 10 minutes in Mammalian Liver Cells

 

If a Cell is Deprived of Nutrients, the Level of ..........................................

 

The Cell Thereby Obtains Extra Energy by Breaking Down Some of its ...........................

 

Once the Digestive Process of the Autophagolysosome is Completed, the Organelle is Termed a ...................................

 

Depending on the type of Cell the Residual Body may be .............................................. by Exocytosis

 

Alternatively it May be Retained Within the Cytoplasm as a ......................................

 

.......................................... Increase in Cells as they Age and are Particularly Evident in Long-Lived Cells Such as Neurons

 

......................................... are Considered a Major Characteristic of Aging

 

Plant Vacuoles

 

 

As Much as 90 Percent of Plant Cells is Occupied by a Single Membrane-Bound, Fluid-Filled ..........................................

 

Many Cell Materials, Ions, Sugars, Amino Acids, ..........................................., are Stored Temporarily in Vacuoles

 

Vacuoles Store a Range of ..................................... that are Often Part of the Cells Defence System and are Released when the Cell is Damaged by an Herbivore or Fungus

 

Other Toxic Compound are Merely By-Products of .............................

 

Plants Lack the Excretory Systems of Animals and so Seek to ............................ Products from the Rest of the Cell

 

Some Plant Products, Such ..........................., Form Useful Medical Compounds

 

The Vacuole Membrane, is Called ...............................

 

The Tonoplast Contains a Number of ...........................................Systems that Pump Ions into the Vacuole to a Much Higher Concentration than in the Cytosol

 

Water then Enters the Vacuole by ......................

 

The ................... (Hydrostatic) Pressure that Developes from this, Provides Mechanical Support for Plant Tissues and Also Stretches the Plant Cell Wall During Cell Growth

 

Like Animal Lysosomes, Vacuoles are Also Sites of ...................................

 

Vacuoles have Homologues of Some Lysosomal Acid ..................................

 

Like Lysosomes, Internal pH is Kept Low by Tonoplast ................................... Pumping Protons into the Vacuole

 

.................................... are Made by the RER, are Processed by the Golgi and are Trafficked to Vacuoles in Vesicles

 

The Endocytic Pathway

 

The Endocytic Pathway Starts with the Invagination of the Plasma Membrane to form ...................................... that are Transported into the Cell

 

The Endocytic Pathway Concerns to Similar Processes, ..................................................

 

Endocytosis is where the Cell Internalizes ................................. and Their Bound Ligands

 

Phagocytosis Involves the ................................... from Extracellular Fluid

 

The Endocytic Pathway: Endocytosis

 

2 Kinds of Endocytosis Exist, Bulk-Phase and Receptor-Mediated ............................

 

Bulk-Phase Endocytosis or ........................., is the Non-Specific Uptake of Extracellular Fluid

 

Any Molecules in the Enclosed Fluid, ...............................

 

Pinocytosis Also Removes Plasma Membrane and Functions Primarily to ....................................Between the Cell Surface and the Interior

 

Receptor-Mediated Endocytosis (RME) Absorbs Specific Macromolecules (Ligands) into the Cell, as they are .......................................... on the Cell Surface

 

Cells have Receptors for Many Types of Ligand Present in the Extracellular Fluid at ............................................

 

These Include ............................................., Enzymes and Blood-Borne Nutrients Carried by Certain Proteins

 

Substances that Enter a Cell by RME, Bind to Receptors that Collect in Specialized Plasma Membrane Domains ................................

 

Receptors in Coated Pits are Concentrated at ........................ their Normal Level in the Rest of the Plasma Membrane

 

At Coated Pit Sites, the Plasma Membrane is Indented and Covered on its Cytoplasmic Face with .....................

 

The Clathrin Coat has a ...................................................

 

Each Clathrin Molecule Consists of 3 Heavy Chains and 3 Light Chains Joined Together to Form a .........................

 

As the Vesicle Forms, the Flat Shape of the ........................................ as it Invaginates

 

As the ..........................., it Restructures and Some of the Hexagons Become Pentagonal

 

The .............................. is a Very Adaptable Structure for Forming Polyhedronal Shapes

 

Like Clathrin Coated Vesicles Budding form the TGN, Endocytic Vesicles Also have a Layer of ................................ Between the Clathrin and the Vesicle Membrane

 

Unlike the GGA Adaptors, These AP2 Adaptors are a ..................................................., Consisting of .........................

 

The ................. Engages the Cytoplasmic Tails of Specific Plasma Membrane Receptors Leading to their Concentration (and their Bound Ligands) in the Vesicle

 

The ............................................ Binds and Recruits the Clathrin Molecules Overlying the Adaptors

 

Unlike COPI and COPII Vesicles, Endocytic Vesicles are Complex and have a Dynamic Network of Up to .......................................................

 

The ................................. have a Poorly Understood Role in Cargo Recruitment, Coat Assembly, Membrane Invagination, Interaction with the Cytoskeleton, Vesicle Release and Membrane Uncoating

 

............................is a G-Protein Required for the Release of Clathrin-Coated Vesicles from the Plasma Membrane

 

..................Self-Assembles into a Helical Collar Around the Neck of the Invaginated Coated Pit, Just Before it Pinches Off from the Membrane

 

Hydrolysis of GTP Bound to Dynamin Induces a ...................................... that Severs the Vesicle from the Membrane

 

Dynamin May Sever the Membrane Connection Directly or Through the Action of Another .................................

 

If a ................................................. of GTP is Bound to Dynamin, It Continues to Build the Helical Ring of Dynamin Subunits Without Severing Off the Vesicle

Within a Minute of Separation from the Membrane the Vesicle Loses its Clathrin Coat and Enters the Endocytic Pathway

 

There are 2 Types of Receptors that Utilize the ..................................., House Keeping Receptors that Bring Nutrients into the Cell and Signaling Receptors

 

Housekeeping Receptors, Including the .......................................... Receptors Bringing Iron and Cholesterol into the Cell

 

The Signaling Receptors Carry Ligands, such as .......................................... such as EGF that Bind to these Surface Receptors

 

The Hormones and Growth Factors Enter the Cell and Signal that a ................................................... is Required

 

Once the Housekeeping Receptors have Delivered their Cargo to the Cell, they are .............................................................. for Additional Rounds of Uptake

 

Signaling Receptors are Often Destroyed After Use and this is Known as ...................................................

 

Receptor Down-Regulation Reduces the Sensitivity of the Cell to Stimulation by ......................................................................

 

Signaling Receptors are Marked for Endocytosis and Destruction by the Addition of a ..................................................... of the Receptor

 

The Tag is .........................., a Small Protein that is Added Enzymatically

 

Membrane Proteins Not Normally Subject to Endocytosis, Become Endocytosed if ...............................................

 

Following Endocytosis, Vesicles ....................................... in the Endocytic Pathway

 

The Lumen of Endosomes is Acidified by ............................... in the Membrane

 

Endosomes are Divided into 2 Distinct Classes.................................. Near the Periphery of the Cell and ....................................... Closer to the Nucleus

 

................................ Endosomes Can be Distinguished by their Bouyant Density, pH and Protein Composition

 

Late Endosomes may Also have ...........................................

 

The Early Endosomal Compartment Serves as a Sorting Center for Receptors and Ligands which are Sent Along ....................................

 

Housekeeping Receptors are Dissociated from their Ligands by the ......................................................... of the Early Endosomal Lumen

 

Housekeeping Receptors are then Concentrated in Specialized .......................................... and Recycled Back to the Plasma Membrane in Vesicles

 

In Contrast, Ligands are Concentrated into a Sorting Compartment Before Being Dispatched to a ................................. and then a Lysosome where Final Processing Occurs

 

The Endocytic Pathway: LDL and Cholesterol

 

Cholesterol is Used by Animals in the ........................................ and as a Percursor of Steroid Hormones

 

Cholesterol is Hydrophobic and is Transported in the Blood in Huge Lipoprotein Complexes Such as LDL .......................................................

 

Each LDL has a Core of Around 1500 Cholesterols Esterified to .................................

 

The Cholesterol Core of LDL is Surrounded by a Single Layer of ........................and a Single Copy of a Large Protein Called ......................................

 

The Apolipoprotein B-100 Specifically Binds to ....................... on the Surface of Cells

 

LDL Receptors on the Plasma Membrane get Concentrated in .........................

 

Once .................................................. in the Coated Pit, the Pit Invaginates to Form a Coated Vesicle, the Clathrin Disassembles and the LDL Receptors are Recycled Back to the Membrane

 

The LDL Particles are Delivered to the ..................... where the Protein Coat is Degraded, the Cholesterol is De-Esterified and Used by the Cell in Membranes or in Metabolism

 

People with the Rare Inherited Disorder, ........................................, Lack a Lysosomal Cholesterol Transfer Protein, so it Accumulates Inside Lysosomes

 

This Accumulation Leads to ............................................. and Death in Childhood

 

The Level of Blood LDL Correlates with Development of ...............................

 

This Leads to the Formation of ....................................... that Restrict Blood Flow and Act as Sites For Formation of Blood Clots

 

Blood Clots Block Coronary Arteries Causing ...................................... (Heart Attack)

 

................................ Stems from an Inflammatory Response Initiated by Deposition of LDL on the Inner Walls of Blood Vessels

 

Lowering Blood LDL Levels Can be Achieved Using Drugs Called ...............(Lovastatin or Pravastatin) that Block HMG CoA Reductase a Key Enzyme in Cholesterol Synthesis

 

..................................... Levels Reduce the heart Attack Risk

 

The Endocytic Pathway: HDL and Cholesterol

 

As well as LDL there is Also HDL (.......................................) in the Blood

 

HDLs are Like LDLs in Structure Except their Apolipoprotein is of the ................

 

 LDL Carries Cholesterol from the .......................................... to the Rest of the Body

 

HDL Carries Cholesterol in the ........................................

 

....................................... is Transported Out of the Plasma Membrane of Cells to Circulating HDL which Carries it on to the Liver

 

High HDL Levels are Associated with a ................................................

 

However, Cholesterol Homeostasis is Not Simple as it ..................................... from HDL to LDL by an Enzyme Called Cholesteryl Ester Transfer Protein (CETP)

 

................................. Tends to Lower HDL Levels

 

A Group of Japanese Families with a ................................. live more than 100 Years on Average

 

A ...................... has Been Developed Against CETP to Try to Mimic the Effect of the Mutation

 

Currently the Vaccine is in ................................................

 

The Endocytic Pathway: Phagocytosis

 

Phagocytosis is Carried Out by a Few Cell Specialized for the Uptake of ....................... (>500nm)

 

Single-Celled Protists ................................., Folding them into a Vacuole (Phagosome), Using the Plasma Membrane

 

The Phagosome Fuses with a Lysosome and Food is Digested in this ...........................

 

In Most Animals, Phagocytosis is an .............................................

 

................................................. Phagocytose Invading Organisms, Dead Cells or Cell Debris

 

These Materials are Recognized by ........................................

 

.................................................. may be Killed by Lysosomal Enzymes or Oxygen Free Radicals Generated in the Lumen of the Phagosome

 

Engulfment of Materials Involves the Activities of .......................................... Underneath the Plasma Membrane

 

Some Bacteria Hijack the ....................................... as Part of their Survival Strategy

 

Mycobacterium tuberculosis is Taken into Macrophages by Phagocytosis, but the Phagosomes ............................ with a Lysosome

 

The Bacteria Inhibits Membrane Fusion and Instead .........................................

 

In Contrast, the Bacterium Responsible for Q Fever, Coxiella burnetii, Becomes Enclosed in the Phagosome, but Neither the ...................................................................................................... Can Destroy it

 

Listeria monocytogenes, a Bacterium that Causes Meningitis, Produces Proteins that Destroys the .........................................

 

This Allows the Bacterium to Escape into the ..................................

 

Protein Uptake in Other Organelles

 

Proteins Destined for Other Organelles Such as Mitochondria, Plastids, Peroxisomes and the Nucleus have to be ...........................................................

 

The Proteins Destined for these Cells Contain Sequences which are Recognized by ..........................................................................

 

The Proteins Concerned are ............................................... in the Cytosol Before Being Imported into the Various Organelles

 

Import of Proteins into the ................... is a Separate Topic which will be dealt with Later

 

Protein Uptake in Peroxisomes

 

Proteins Imported into Peroxisomes are Destined Either for the ....................................................................

 

They have a ........................................................., with is Either a PTS for the Internal Matrix or an mPTS for the Membrane Proteins

 

Several Different PTSs, mPTSs and ................................. have been Discovered

 

PTS Receptors Bind to PTS or mPTS Protein in the Cytosol and ............................. the Peroxisome

 

The Receptors Accompany the Proteins Across the Membrane into the Peroxisomes and these Proteins are Kept in their ................................................. During the Process

 

Protein Uptake in Mitochondria

 

As Mitochondria have a ................................, they have 4 Sub-Compartments Proteins Need to be Delivered to, The Outer Membrane (OMM), the Inner Membrane (IMM) the Intermembrane Space and the Matrix

 

Mitochondria have DNA that Encodes (and is Used to make) a Few of their Own Membrane Proteins (13 in Mammals), the Other 95% of Proteins are Encoded by the Nucleus and made in the Cytosol and .........................................

 

Mitochondrial Proteins Contain .............................. that Target them to this Organelle

 

Mitochondrial ................... Proteins Contain a Removable Presequence at the N-Terminal which has a Number of .............................................................

 

IMM Proteins Contain an ........................................ which Remains Part of the Molecule

 

Before a Protein Can Enter the Mitochondrion, it must be Relatively ........................

 

Chaperones have been Implicated in the Preparation of Proteins for Entry, Especially Directing Protein to the ...........................................

 

The OMM Contains a Protein Import Complex Called the .................................

 

The TOM Complex, Includes Receptors that ............................. Mitochondrial Proteins

 

It Also has ................................. Through which Unfolded Proteins Are Moved Across the OMM

 

Proteins Destined for the IMM, must Cross the ............................... Before Interacting with a Second Import Complex, the .........................

 

The IMM Contains ..............................................:

 

...............which Binds Integral Membrane Proteins

 

................ which Binds Matrix Proteins and Translocates them Through the IMM into the Matrix Compartment

 

Translocation Occurs at Sites where the ................................ are Close Together so that the Imported Protein can Cross Both Membranes Simultaneously

 

Movement of Proteins into the Matrix is Powered by the .................................... Across the .............

 

This Attracts the ..............................................................in the Proteins Signal Sequence

 

If the Potential is Dissipated Using the Drug DNP, ............................................

 

As the Proteins Enter the Matrix they Interact with Chaperones Such as ...................

 

The Chaperones May Act as a Motor to ...................... Through the Translocation Pore

 

Or Chaperones May Merely Aid the ........................of the Protein Across the Membrane

 

However, the Chaperones in the Matrix May Act to Block Diffusion of Proteins ....................................................., Only Letting them Forward into the Matrix (Known as Biased Diffusion)

 

Once Proteins Enter the Matrix the Signal Presequence is Removed by the Mitochondrial ....................................................... (MPP)

 

Protein Uptake in Chloroplasts

 

Chloroplasts have .............................. to which Proteins have to be Delivered, the Inner and Outer Membranes and the Intermembrane Space, the Stroma, The Thylakoid Membrane and the Thylakoid Lumen

 

Chloroplast Protein Import Mechanisms are Similar to those in ............................

 

                        1) Most Chloroplast Proteins are .......................from the Cytosol

 

2) The Inner and Outer Membrane Contain Distinct .............................................. (Toc and Tic) that Work Together During Import

 

                        3) ............................... Aid in the Unfolding of Proteins in the Cytosol and the Folding in the Chloroplast

 

                        4) Protein Destined for the Chloroplast are Synthesized with a Removable N-Terminal Sequence (the ...................................)

 

The ................................... Provides Both Targeting to the Chloroplast and to the Sub-Compartments Within

 

All Proteins Translocated Through the Double Membrane Contain a ......................................................... as Part of the Transit Peptide

 

Once in the Stoma this Domain is Removed by a ........................................... Enzyme

 

Thylakoid Proteins have an Additional Segment in the Transit peptide, Known as the ...........................................................

 

The Pathways that Determine Whether a Thylakoid Protein is Transported to the Membrane or the Lumen are Similar to ..................................................

 

Many ..................................................... are Encoded by Chloroplast DNA and are Translated by Membrane-Bound Ribosomes in this Membrane