| First Author | Nakano-Kobayashi A | Year | 2007 |
| Journal | EMBO J | Volume | 26 |
| Issue | 4 | Pages | 1105-16 |
| PubMed ID | 17290217 | Mgi Jnum | J:120101 |
| Mgi Id | MGI:3703857 | Doi | 10.1038/sj.emboj.7601573 |
| Citation | Nakano-Kobayashi A, et al. (2007) Role of activation of PIP5Kgamma661 by AP-2 complex in synaptic vesicle endocytosis. EMBO J 26(4):1105-16 |
| abstractText | Synaptic vesicles (SVs) are retrieved by clathrin-mediated endocytosis at the nerve terminals. Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] drives this event by recruiting the components of the endocytic machinery. However, the molecular mechanisms that result in local generation of PI(4,5)P2 remain unclear. We demonstrate here that AP-2 complex directly interacts with phosphatidylinositol 4-phosphate 5-kinase gamma661 (PIP5Kgamma661), the major PI(4,5)P2-producing enzyme in the brain. The beta2 subunit of AP-2 was found to bind to the C-terminal tail of PIP5Kgamma661 and cause PIP5Kgamma661 activation. The interaction is regulated by PIP5Kgamma661 dephosphorylation, which is triggered by depolarization in mouse hippocampal neurons. Finally, overexpression of the PIP5Kgamma661 C-terminal region in hippocampal neurons suppresses depolarization-dependent SV endocytosis. These findings provide evidence for the molecular mechanism through which PIP5Kgamma661 locally generates PI(4,5)P2 in hippocampal neurons and suggest a model in which the interaction trigger SV endocytosis. |
