title: ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma.
abstract: Clathrin-mediated endocytosis of synaptic vesicle membranes involves the recruitment of clathrin and AP-2 adaptor complexes to the presynaptic plasma membrane. Phosphoinositides have been implicated in nucleating coat assembly by directly binding to several endocytotic proteins including AP-2 and AP180. Here, we show that the stimulatory effect of ATP and GTPgammaS on clathrin coat recruitment is mediated at least in part by increased levels of PIP2. We also provide evidence for a role of ADP-ribosylation factor 6 (ARF6) via direct stimulation of a synaptically enriched phosphatidylinositol 4-phosphate 5-kinase type Igamma (PIPKIgamma), in this effect. These data suggest a model according to which activation of PIPKIgamma by ARF6-GTP facilitates clathrin-coated pit assembly at the synapse.
authors.affiliation: Zentrum für Biochemie und Molekulare Zellbiologie, Dept. of Biochemistry II, University of Göttingen, Humboldtallee 23, Göttingen D-37073, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Krauss
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kinuta
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: Kohji
authors.initials: K
authors.lastname: Takei
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D019556:COS Cells; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000201:enzymology*; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013570:Synaptic Membranes / Q000201:enzymology*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000201:enzymology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000089982:ADP-Ribosylation Factor 6; D033962:Adaptor Protein Complex 2; D002966:Clathrin; D008081:Liposomes; C100530:PIP2 protein, S cerevisiae; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D020126:Brefeldin A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D020727:ADP-Ribosylation Factors