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Vesicle Formation at the Plasma Membrane and Trans-Golgi Network: The Same but Different

Vesicle Formation at the Plasma Membrane and Trans-Golgi Network: The Same but Different. M. A. McNiven, et al., Science 313 , 1591 (2006)

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Vesicle Formation at the Plasma Membrane and Trans-Golgi Network: The Same but Different

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  1. Vesicle Formation at the Plasma Membrane and Trans-Golgi Network: The Same but Different M. A. McNiven, et al., Science 313, 1591 (2006) Department of Biochemistry and Molecular Biology and the Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine, Rochester Liangfang Zhao, Yanqing Lin & Zhiling Yao Life Science College, CNU 2007.10.30

  2. Abbreviations • PM: Plasma Membrane • TGN: Trans-Golgi Network • CCV: Clathrin-Coated Vesicle • APs: Adaptor Proteins • EGF: Epidermal Growth Receptor • GGAs: Golgi-localized, γ-earcontaining, Adenosine diphosphate Ribosylation Factor (ARF) • PIP2:PhosphatidylInositol4,5-bisPhosphate • PI4P:PhosphatidylInositol4-monoPhosphate • UIMs:Ubiquitin Interacting Motifs

  3. Overview: yin & yang relationship • Sorting, packaging, vesiculation, transport of membrane and protein cargo active exchange of membranes & protein cargo; highly conserved mechanisms in vesicle formation & scission • In and out of the cell • Membrane continuum

  4. Index • I. similarities and variations in sorting mechanisms • II. Lipid-membrane binding, bending and pinching • III. Vesicle scission

  5. I. similarities and variations in sorting mechanisms • Similarities in protein-sorting mechanisms at the PM and TGN • Variations of a common sorting machine

  6. 1.Similarities in protein-sorting mechanisms at the PM and TGN • Key functions: selective sequestration and packaging of protein cargo • Central scaffold: clathrin and its associated coat proteins

  7. APs and monomeric clathrin-associated sorting proteins • “first line” of cargo-sequestration specificity • AP1-4 similar organization, subunits, structure; different cellular localization patterns, vesicle-formation processes

  8. AP: mediate protein sorting • Recognition of sorting motifs of the cytosolic domains of transmembrane proteins • Three classes Asn-Pro-X-Tyr: AP-2 at the PM while interact with non-AP-2 Tyr-X-X-Φ: μsubunit of all 4 APs [Asp-Glu] X-X-X-Leu [Leu-Ile]: AP1-3 yet different preferences

  9. Conclusion for PART 1 Different affinities between leaving and being internalized

  10. 2.Variations of a common sorting machine • Several layers of regulation and targeting: provide specificity • Different lipids & phosphoinositides; small GTPases; GGAs

  11. Lipids • Cholesterol, sphingoipids, phosphoinositides • Rafts (lipid microdomains) mediate clathrin-independent vesicle formation participate in sorting at the TGN ratio differ: maintain the participation of membrane microdomains • Form vesicle: inositol phospholipids different combinations of phospho-modifications: PIP2 & PI4P(LESS TIDY)

  12. Same phosphoinositide: essential in multiple distinct vesicle formation processes at both sides

  13. Small GTPases • Regulate secretory & endocytic vesicle formation • TGN targeting of AP-1: Active ARF1 & Golgi-enriched PI4P • PM CCV formation: ARF family dependent in some cases

  14. GGAs: function along with the AP-based sorting system • Recruitment to Golgi: ARF dependent • Generate CCVs’ subset which targets to lysosomes: function along with AP-1 • Mediate sorting of lysosome-targeted proteins: bind to different dileucine motifs AP-1: [DE]XXXL[LI] GGAs: Asp-X-X-Leu-Leu

  15. Ubiquitin modification • TGN: Initiate nascent proteins sorting • PM: Sort endocytosed proteins to endosomes & lysosomes • At both vesicle-formation sites: PM: Eps15 & Epsin----sequester & sort activated EGF receptors bind each other & AP-2 contain UIMs TGN: GGAs & Eps15 Eps15: AP-1

  16. costain

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