Professor Ugalde Lecture 13 Flashcards
What is the purpose of the lysosome?
-recycle bin of the cell, and it has a low pH
ex. proteins that need to be recycled into amino acids
What do MVBs fuse with to become lysosomes?
-MVBs fuse with vesicles containing proteases and other enzymes to become lysosomes
What is the lysosome a site for?
Why does it have a low pH?
-after the ER, the lysosome is the final state of protein degradation in the secretory pathway
-Lysosome is highly acidic with pH 5 causing normal proteins to unfold and lysosomal enzymes are most active at low pH
How is low pH of lysosome maintained?
Where is the broken down products returned?
-low pH maintained by an ATP-dependent proton pump
-final breakdown products are returned to cytosol by small-molecule transporters
What is the model for lysosome maturation?
late endosome–>endolysosome–>lysosome
What is autophagy?
When is it upregulated?
Where are lipids and proteins transported through?
-large scale digestion of cytosol and membranes
-upregulated during starvation to release free amino acids
-lipids and proteins are transported through cytosol to form phagophore vesicle
What does phagophore vesicle do in autophagy
-What does autophagosome fuse?
-phagophore grows to enclose contents in an autophagosome which is double membrane and varies in size
-autophagosome fuses with lysosome to digest contents
What is selective autphagy?
What are the receptors for?
What is this an alternative for, what type of Ub chain is preferred?
-cargo receptors attach selected substrates to the phagophore
-receptors for mono and poly UB proteins
-alternative to proteasome mediated degradation
-K63 (lysine) poly-uB chains preferred instead of K48 poly-UB (used for proteasome)
What happens in CMA (chaperone mediated autophagy), what does HSP70 do?
What does HSP70 bind to?
- HSP70 recognizes a specific domain and brings it to surface of lysosome
- HSP70 binds the subtrate to the cytosolic tail of the receptor protein LAMP-2A which promotes LAMP-2A multumerization to form translocation complex
What happens upon unfolding in CMA after LAMP-2A multimerizes?
4. What aids the protein in the previous step, what does it reach?
Upon unfolding, substrate proteins cross the lysosomal membrane
4.it is assisted by a luminal chaperone and reaches the lysosomal matrix where they undergo complete degradation
What happens after stimulation in synaptic vesicles?
-in the presynaptic cleft there are vesicles that are fusing to the membrane to release cargo upon stimulation (releases neurotransmitter)
How does ultrafast endocytosis compare to normal endocytosis?
Why is this method faster?
-there are larger vesicles formed that are the area of 4 synaptic vesicles
-not all the vesicles being formed are CCV, some endocytic vesicles were foming faster than CCV
