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68 Cards in this Set

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  • Back
What is the crucial event in secretion?
Fusion of membrane vesicles that budded from the golgi, with the plasma membrane.
What type of secretion occurs in pancreatic exocrine cells?
Regulated secretion
What is unregulated secretion called?
Constitutive secretion
Does membrane fusion only occur during exocytosis?
No - obviously it happens within the golgi complex etc.
What do we best understand membrane fusion for?
Viruses - like the flu virus
How does the flu virus enter cells?
By fusing its membrane envelope with the plasma membrane.
What mediates this membrane fusion?
Fusion proteins - Hemagglutinin
What is created by the fusion proteins being inserted in a target cell?
A protein bridge which brings the virus/cell into close proximity.
What brings about the actual fusion?
Conformational change in the protein complex.
What are the membrane fusion proteins that mammalian cells use for fusion?
How do SNARES work?
-Form large protein complexes at membrane docking sites
-Bring adjacent membranes into close proximity for fusion
Do membranes fuse randomly?
What regulates membrane fusion and provides specificity?
RAB PROTEINS - GTP binding proteins
Which RAB protein regulates exocytosis at the plasma membrane?
what one regulates fusion between golgi and lysosomes?
Rab 7
How do GTP proteins function?
By cycling between GTP and GDP bound states
What are the 2 big things that happen when a membrane vesicle fuses with the plasma membrane?
1. Its contents are released
2. Its membrane fuses with the plasma membrane and gets INCORPORATED INTO IT
What are the consequences of the membranes fusing?
It increases the surface area of the cell - though not a lot.
What compensates for the increased SA?
Simultaneous endocytosis.
Why exactly do we need fusion proteins again?
Because cell membranes are neg charged and repel; need to bring them close together before they will run together like salad dressing.
When are RAB proteins in their active state and able to bind fusion complexes?
When bound to GTP
When are RAB proteins in their inactive state?
When bound to GDP
Fundamental feature of lysosomes and endosomes:
Acidic pH
How do lyso/endosomes get their pH acidic?
By proton pumps
What can be used to identify lyso and endosomes?
Chloroquine - they accumulate this weak base.
What are endosomes associated with?
3 types of endocytosis:
What type of endocytosis is phagocytosis?
What receptor is used in phagocytosis by macrophages?
Fc receptor
What is involved in Fluid phase endocytosis?
Uptake of components in the fluid phase that are not bound specifically to the membrane
What marker is used to study fluid phase endocytosis?
Horseradish peroxidase
What did bersharse show in his lab about macrophage and Lcell endocytosis via horserad peroxd?
Turnover rate of entire membrane
-Macrophages were every 32 min
-Lcells once every 111 min
How does receptor mediated endocytosis compare to fluid phase?
It is more specific
What is the classic example of receptor mediated endocytosis?
What happens when LDL binds its LDL receptor?
The complex is internalized to form a COATED (clathrin) vesicle
Where does the coated vesicle go?
To fuse with an endosome and be uncoated
What happens to the LDL receptor after LDL comes off?
It's recycled to the cell surface.
What are the protein complexes formed by clathrin called?
What links the clathrin coat to the pit that is the membrane domain of the receptor?
Adaptin proteins
What are the 2 fundamental pathways of protein degradation?
1. Lysosomal
2. Ubiquitination
What is the purpose of lysosomes?
To degrade their components with hydrolytic enzymes
How does stuff get into lysosomes?
By endocytosis
What are proteins that enter lysosomes degraded with?
Lysosomal proteases
Where does ubiquitination occur?
In the cytosol
How does the ATP-dependent proteolytic machinery know to degrade proteins?
They are tagged with ubiquitin
Where are lysosomal enzymes made?
In the rough ER, like normal
What happens to lysosomal enzymes at the trans golgi network?
They diverge from the secretory pathway into pleiomorphic organelles called these LYSOSOMES
What needs to be on the enzymes to make them go to lysosomes?
Targeting signals
What cellular organelles have the longest half lifes?
-Mitochondria - 6.8 days
-Nucleus - 5.1 days
What cellular organelle has the shortest half life?
The plasma membrane - 1.8 days
Do lysosomes only contain hydrolases and proteolysing enzymes?
no, they also have phosphatases, lipases, nucleases, sulfatases, glycosidases, and phospholipases
Where do lysosomes form again?
At the trans-golgi network - it buds off just like secretory vesicles.
What ARE lysosomal enzymes?
How does the golgi know not to send lysosomal enzymes to the cell surface?
The core protein put onto the glycoproteins in the RER gets a MANNOSE-6-PHOSPHATE added to it.
Where does the Mannose6P get added?
Between the RER and cis-golgi
What recognizes the Mannose-6P?
M6P-receptor in the golgi complex
Where are lysosomal enzymes first targeted?
To endosomes, then subsequently lysosomes.
What makes the lysosomal enzymes dissociate from their M6P receptors after budding from the trans golgi?
The acidic environment
What is the function of the small amount of M6PR at the cell plasma membrane?
To scavenge any lysosomal enzymes that do escape the normal sorting process.
What are the 2 classic lysosomal storage diseases?
-Icell disease
-Hurler's disease
What is the problem in lysosomal storage diseases?
Lack or deficiency of a lysosomal enzyme
Why are they called storage diseases?
Because the cell is unable to degrade macromolecules and so they accumulate (get stored in) lysosomes.
What enzyme is lacking in Hurler's disease?
What can't people with Hurler's disease break down?
Dermatan sulfate
Symptoms of hurler's disease:
-Growth problems
-Mental retardation
What is lacking in I-cell disease?
All acid hydrolases in lysosomes
Why does Icell disease develop?
The enzyme for phosphorylating mannose to make the mannose-6P marker is missing.
What would happen to newly synthesized lysosomal enzymes in I-cell disease?
They would end up on the cell surface and degrade the extracelular contents - bad.