CFM2: Golgi

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CFM2: Golgi
2015-09-07 15:44:22
cfm cfm2

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  1. COPII vesicles are made in the _______
    Smooth ER
  2. COPI and COPII vesicles
    • Transport between ER and Golgi
    • COPI: Retrieval pathway (Golgi --> ER)
    • COPII: Forward pathway (ER --> Golgi)
  3. ERGIC: What is it and what happens when mutated?
    • Protein that recognizes 2 clotting factors in the liver and helps these clotting factors get into COPII vesicles
    • Mutation causes mild form of hemophilia because these clotting factors are not secreted well
  4. ER membrane proteins that are receptors for cargo destined for the Golgi, or are themselves cargo destined for the Gogli, recruit COPII by ________
    diacidic amino acid sequences in their cytoplasmic tails
  5. ER membrane proteins that need to be returned to the ER recruit COPI by ________
    sequence of basic amino acids in cytoplasmic tail
  6. KDEL
    Sequence of amino acids on C-terminus of ER resident proteins; recognized by KDEL receptor in COPI vesicles to bring these proteins back to the ER from the cis-Golgi
  7. KKXX
    Amino acid motif on cytosolic side of KDEL receptor, or on the cytosolic side of ER-resident membrane proteins; recruits COPI
  8. Structure of Golgi apparatus and function of each on modification of glycoproteins
    • Cis Golgi Network (CGN): COPII vesicles fuse and COPI vesicles form
    • Cis cisternae: trimming of mannose residues; synthesis of man-6-P markers on lysosomal hydrolases
    • Medial cisternae: addition of N-acetyl glucosamine
    • Trans cisternae: addition of galactose and sialic acid
    • Trans Golgi Network (TGN): Final site of sorting and vesicle exit; furin-mediated cleavage of some proproteins
  9. How does sialic acid affect the charge of glycoproteins?
    Located on the end of glycoproteins; sialic acid is negatively charged, so most glycoproteins are negatively charged
  10. O-linked glycosylation
    Glycosylation of lipids or proteins; in case of proteins, sugars bound to hydroxyl groups of serine or threonine; ex: ABO blood groups
  11. Furin
    • Enzyme in membrane of TGN; cleaves certain proproteins at certain dibasic amino acid sequences
    • Ex: HIV160, insulin receptor
  12. 3 pathways for proteins to go after being released from Golgi
    • Constitutive secretory pathway: goes straight from Golgi to plasma membrane
    • Regulatory secretory pathway: stored in secretory granule until needed (ex: insulin needed in fed state)
    • Endosome/lysosome pathway
  13. Endosome/lysosome pathway mechanism
    • Lysosomal enzymes
    • Phosphotransferase catalyzes modification that makes a mannose-6-phosphate on the enzyme of interest
    • Recognized by M6P receptor in trans-Golgi, which have clathrin-coated vesicle recruitment signals on cytoplasmic tail
    • Adaptor proteins bind M6PR, recruiting clathrin
    • Clathrin-coated vesicle buds off and goes to endosome
    • Low pH of endosome allows cargo protein to be released into endosome; vesicle recycled.
  14. Regulated secretory pathway
    • Immature granules form when a large segment of the TGN containing condensed material pinches off the Golgi, which is mildly acidic
    • Granule content aggregates at this acidic pH, and the pH of the immature granule drops further, inducing more aggregation
    • Excess membrane of IG removed by clathrin-coated vesicles, leaving a mature granule
  15. Prohormone convertases
    Enzymes that activate certain proteins from their proprotein forms
  16. Rab proteins: what are they and how do they work?
    • Docking proteins
    • GTPases
    • When Rab binds GTP, it latches on to a forming vesicle
    • Rab effector binds to rab protein on target membrane; GTP hydrolyzed
  17. SNAREs
    • vSNAREs on vesicles, tSNAREs on target membrane
    • SNARE pairs are specific to each other
  18. Synaptotagmins
    • Located in synaptic terminal in axon
    • Block vSNAREs on synaptic vesicles
    • After action potential, calcium influx
    • Calcium binds to synaptotagmin, exposing vSNARE, allowing exocytosis of neurotransmitter
    • Synaptotagmins also have phospholipid binding elements
  19. How does Botox treat migraines?
    • Botox is a protease that inhibits synaptic transmission by cleaving SNAREs
    • No vesicle fusion, no neurotransmitter release, muscles are relaxed