Week 7 Flashcards
Two models for the mechanism of protein transport from the cis-Golgi to the trans-Golgi network (TGN)
- Vesicular transport between stationary cisterna
- Cisternal maturation
Which model for the mechanism of protein transport from the cis-Golgi to the trans-Golgi network (TGN) is more favored?
The cisternal maturation model.
In the vesicular transport model, what is required for bringing proteins from one cisternae to the next?
Intermediate COPI vesicles.
What does the signaling pathway of secretory (exocytic) vesicles typically lead to?
The signaling pathway typically leads to the opening of a calcium channel and influx of calcium into the cytosol.
Role of beta cells
Insulin is secreted by beta cells in the pancreas
When does prohormone processing occur?
Prohormone processing occurs during vesicle formation and maturation
Which coat protein is involved in the maturation process (recycling of prohormone convertases)?
Clathrin
What do beta cells measure?
Blood glucose concentration (should be about 3 mM at a fasting concentration)
Series of events that occurs after glucose enters the cell.
- The mitochondria will make ATP
- The ATP will bind to the K ATP channel, causing it to close.
- The membrane potential will fall.
- Depolarization of the membrane.
- Calcium enters the cell
- This stimulates exocytosis of insulin into the bloodstream.
What type of cellular structures are required for the final step of secretion (exocytosis)?
This process requires tethers, Rabs, and SNAREs.
What do regulated vesicles typically require to drive SNARE-dependent fusion?
- Regulated vesicles typically require a calcium influx to drive SNARE-dependent fusion.
- Constitutive vesicles also use SNAREs to drive membrane fusion but do not need calcium.
What process does synaptotagmin play a role in?
The regulation of synaptic vesicle fusion by calcium and synaptotagmin
Two routes that proteins can take to get to the apical surface
- Direct sorting of membrane proteins in the trans Golgi network
- Indirect sorting via endosomes
Rafts
Cholesterol-sphingolipid rich microdomains within the lipid bilayer.
How do rafts move within the cell?
They are presumably formed in the Golgi and preferentially enter vesicles at the TGN that are targeted to the apical membrane.
The raft hypothesis
The raft hypothesis proposes that certain proteins tend to partition preferentially into the cholesterol-sphingolipid rich raft domains. For example, proteins with longer transmembrane domains may prefer to stay in parts of the membrane that are thicker because of the abundance of cholesterol and sphingolipid. Sphingolipids tend to have longer (20 - 24 carbon) acyl chains that are typically saturated.
Signaling and processes associated with the ER
- Cleavable signal sequence
- SRP, translocon
- Folding, N-glycosylation
- Sorting into COPII vesicles
Signaling and processes associated with the Golgi
- Mannose-6-phosphate (M6P)
- Cisternal maturation
- M6P receptor
- Clathrin-coated vesicle
Signaling and processes associated with the late endosome
- Dissociation from receptor
- Recycling of receptor
Signaling and processes associated with the lysosome
Fusion with late endosome
Three different kinds of vesicles being generated from the TGN
- Signal-mediated diversion to lysosomes
- Constitutive secretory pathway
- Signal-mediated diversion to secretory vesicles (for regulated secretion)
What does recognition of a signal patch common to multiple lysosomal enzymes lead to?
Their modification with mannose-6-phsophate.
I-cell disease
I-cell disease is a severe lysosomal storage disorder caused by deficiency of the GlcNAc phosphotransferase. Many soluble lysosomal enzymes are inappropriately secreted in these patients.
Where is the GlcNAc phosphotransferase localized to? What happens as a result?
The cis-Golgi. Lysosomal enzymes receive Man-6-P instead of complex N-linked oligosaccharides.