Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2
| Autor: | Olga Vorontsova, Volker Haucke, Kira Gromova, Michael A. Cousin, Georg Krainer, Ardeschir Vahedi-Faridi, Arndt Pechstein, Jelena Bacetic, Simen Gylterud Owe, Nikolay Tomlin, Johannes G. Schäfer, Oleg Shupliakov, Anna Sundborger, Wolfram Saenger |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Clathrin adaptor complex Endocytic cycle Molecular Sequence Data Adaptor Protein Complex 2 Nerve Tissue Proteins Clathrin Clathrin coat src Homology Domains Membrane fission Synaptic vesicle recycling Animals Amino Acid Sequence Multidisciplinary Binding Sites biology Clathrin coat assembly Sequence Homology Amino Acid appendage endocytosis scaffolding proteins synaptojanin synapse food and beverages Lampreys Biological Sciences Endocytosis Phosphoric Monoester Hydrolases Cell biology Adaptor Proteins Vesicular Transport biology.protein Clathrin adaptor proteins Synaptic Vesicles |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 107(9): 4206–4211 |
| Popis: | Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P 2 ]-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. |
| Databáze: | OpenAIRE |
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