Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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 showthat 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.
Язык оригинала | английский |
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Страницы (с-по) | 4206-4211 |
Число страниц | 6 |
Журнал | Proceedings of the National Academy of Sciences of the United States of America |
Том | 107 |
Номер выпуска | 9 |
DOI | |
Состояние | Опубликовано - 2 мар 2010 |
Опубликовано для внешнего пользования | Да |
ID: 40830427