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