4 5 bisphosphate regulates clathrin coated pits 20 Figure

4 5 bisphosphate regulates clathrin coated pits 20

This preview shows page 20 - 42 out of 75 pages.

Phosphatidylinositiol-(4-5)-bisphosphate regulates clathrin coated pits 20 Figure 13-10a, b, c Molecular Biology of the Cell (© Garland Science 2008) phosphatidylinositol Phosphatidylinositol-(4,5)- bisphosphate a.k.a. PIP2 - Highly enriched at the plasma membrane - Allows AP (adaptor proteins) and dynamin to bind membrane
Phosphatidylinositol-4,5-bisphosphate (PIP2) controls “Opening” of AP2 PIP2
Phosphoinositides Mark Organelles and Membrane Domains
Membrane-Bending Proteins Help Deform the Membrane During Vesicle Formation
Membrane-Bending Proteins Help Deform the Membrane During Vesicle Formation
Monomeric GTPases Control Coat Assembly
26 3-73 The Molecular GTPase Switch (recap) GEF: guanyl exchange factor Loads GTPase with GTP: activates GAP: GTPase activating protein Induces GTPase to hydrolyse GTP to GDP: inactivates
27 Sar1 GTPase Regulates Assembly of COPII Coat on the ER Membrane COPII is involved in forward membrane trafficking from ER to Golgi It helps to deliver new synthesized proteins and lipids to the Golgi
28 Sar1 GTPase Regulates Assembly of COPII Coat on the ER Membrane Sar1-GEF displaces GDP from inactive, cytosolic Sar1-GDP GTP loads onto Sar1 Sar1-GTP exposes amphipathic helix Sar1-GTP binds strongly to ER membrane
Sec23/24 (Yellow) inner coat Sec13/31 (blue- green) outer coat 29
30 Regulation Cargo selection and enrichment Coat proteins required Clathrin-coated vesicles Location at which they are formed COPII vesicles Endoplasmic reticulum Plasma membrane (also: Golgi, endosomes) Location to which they are delivered Many different locations Golgi clathrin Sec23/24 and Sec 13/31 Adaptor protein (AP), bind cargo directly Sec23/24, bind cargo directly Phosphatidylinositol- (4,5)-bisphosphate (a phospholipid) Sar1 (a GTPase)
BTW, Not All Transport Vesicles Are Spherical
32 So you’ve made a vesicle, how does it end up where it’s supposed to?
Rab Proteins Guide Transport Vesicles to Their Target Membrane Transport vesicles must be highly accurate in recognizing the correct target membrane with which to fuse. Rab proteins and Rab effectors direct the vesicle to specific spots on the correct target membrane. SNARE proteins and SNARE regulators mediate the fusion of the lipid bilayers. 33
Rab Proteins Guide Transport Vesicles to Their Target Membrane A specific Rab can be activated either on vesicle or target membrane GTP-bound Rab binds to Rab “effector proteins Rab effector proteins carry out the Rab-regulated function Rab effectors are myriad: enzymes, motor proteins, tethers, etc.
Rab GTPases Are Organelle Specific Rab 5 Early endosomes (Endocytosis – degradation and recycling) Rab 7 and Rab9 Late endosomes (Endocytosis – degradation Rab 1 ER -> Golgi (synthesis) Rab 2 Golgi -> ER (retreival) 36
NAREs Mediate Membrane Fusion The SNARE proteins (also called SNAREs, for short) catalyze the membrane fusion reactions in vesicle transport. Vesicular SNAREs Target SNAREs
Figure 13-16 Molecular Biology of the Cell (© Garland Science 2008) 38 SNARE-mediated membrane fusion between synaptic vesicle and neuronal plasma membrane Many toxins attack these SNARES: botulism and tetanus V-SNAREs : transmembrane, single chain t-SNARES : 2 or 3 chains, at least 1 transmembrane, others may be peripheral membrane proteins
HIV VIRUS ENTERING A CELL

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture