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Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2
- Pechstein, Arndt, Bacetic, Jelena, Vahedi-Faridi, Ardeschir, Gromova, Kira, Sundborger, Anna, Tomlin, Nikolay, Krainer, Georg, Vorontsova, Olga, Schäfer, Johannes G., Owe, Simen G., Cousin, Michael A., Saenger, Wolfram, Shupliakov, Oleg, Haucke, Volker
- Proceedings of the National Academy of Sciences of the United States of America 2010 v.107 no.9 pp. 4206-4211
- Petromyzontiformes, clathrin, deformation, hydrophobicity, inositols, peptides, recycling, synaptic vesicles
- Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P₂]-enriched membrane sites within the periactive zone. Such spatiotemporal control is needed to coordinate SV cargo sorting with clathrin/AP2 recruitment and to restrain membrane fission and synaptojanin-mediated uncoating until membrane deformation and clathrin coat assembly are completed. The molecular events underlying these control mechanisms are unknown. Here we show that the endocytic SH3 domain-containing accessory protein intersectin 1 scaffolds the endocytic process by directly associating with the clathrin adaptor AP2. Acute perturbation of the intersectin 1-AP2 interaction in lamprey synapses in situ inhibits the onset of SV recycling. Structurally, complex formation can be attributed to the direct association of hydrophobic peptides within the intersectin 1 SH3A-B linker region with the "side sites" of the AP2 α- and β-appendage domains. AP2 appendage association of the SH3A-B linker region inhibits binding of the inositol phosphatase synaptojanin 1 to intersectin 1. These data identify the intersectin-AP2 complex as an important regulator of clathrin-mediated SV recycling in synapses.