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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,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,Abbreviations,PM:Plasma Membrane,TGN:Trans-Golgi Network,CCV:Clathrin-Coated Vesicle,APs:Adaptor Proteins,EGF:Epidermal Growth Receptor,GGAs,:Golgi-localized,-,earcontaining,Adenosine diphosphate Ribosylation Factor(ARF),PIP2:PhosphatidylInositol 4,5-bisPhosphate,PI4P:PhosphatidylInositol 4-monoPhosphate,UIMs,:,Ubiquitin Interacting Motifs,Overview:yin&yang relationship,Sorting,packaging,vesiculation,transport of membrane and protein cargo,active exchange of membranes,highly conserved mechanisms in vesicle formation&scission,In and out of the cell,Membrane continuum,Index,I.similarities and variations in sorting mechanisms,II.Lipid-membrane binding,bending and pinching,III.Vesicle scission,I.similarities and variations in sorting mechanisms,Similarities in protein-sorting mechanisms at the PM and TGN,Variations of a common sorting machine,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,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,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-,:,subunit of all 4 APs,Asp-Glu X-X-X-Leu Leu-Ile:AP1-3 yet different preferences,Conclusion for PART 1,Different affinities between leaving and being internalized,2.Variations of a common sorting machine,Several layers of regulation and targeting:provide specificity,Different lipids,GGAs,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:PIP,2,&PI4P(LESS TIDY),Same phosphoinositide:essential in multiple distinct vesicle formation processes at both sides,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,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:DEXXXLLI,GGAs:Asp-X-X-Leu-Leu,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,costain,
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