Cdk5 is essential for synaptic vesicle endocytosis

被引:247
作者
Tan, TC
Valova, VA
Malladi, CS
Graham, ME
Berven, LA
Jupp, OJ
Hansra, G
McClure, SJ
Sarcevic, B
Boadle, RA
Larsen, MR
Cousin, MA
Robinson, PJ
机构
[1] Childrens Med Res Inst, Cell Signalling Unit, Wentworthville, NSW 2145, Australia
[2] Royal Hosp Women, Randwick, NSW 2031, Australia
[3] Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia
[4] Westmead Hosp, Inst Clin Pathol & Med Res, Electron Microscope Lab, Westmead, NSW 2145, Australia
[5] Macquarie Univ, Australian Proteom Anal Facil, N Ryde, NSW 2109, Australia
[6] Univ Edinburgh, Div Biomed Sci, Membrane Biol Grp, Edinburgh EH8 9XD, Midlothian, Scotland
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1038/ncb1020
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Synaptic vesicle endocytosis (SVE) is triggered by calcineurin-mediated dephosphorylation of the dephosphin proteins. SVE is maintained by the subsequent rephosphorylation of the dephosphins by unidentified protein kinases. Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin 1, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE. Thus Cdk5 has an essential role in SVE and is the first dephosphin kinase identified in nerve terminals.
引用
收藏
页码:701 / 710
页数:10
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