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

来源：

NATURE CELL BIOLOGY | 2003年 / 5卷 / 08期

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

页码：701 / 710

页数：10

共 52 条

[1] Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5
Bibb, JA
Chen, JS
Taylor, JR
Svenningsson, P
Nishi, A
Snyder, GL
Yan, Z
Sagawa, ZK
Ouimet, CC
Nairn, AC
Nestler, EJ
Greengard, P
[J]. NATURE, 2001, 410 (6826) : 376 - 380
[2] Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate
Chen-Hwang, MC
Chen, HR
Elzinga, M
Hwang, YW
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (20) : 17597 - 17604
[3] Ca2+ influx inhibits dynamin and arrests synaptic vesicle endocytosis at the active zone
Cousin, MA
Robinson, PJ
[J]. JOURNAL OF NEUROSCIENCE, 2000, 20 (03) : 949 - 957
[4] Synaptic vesicle endocytosis - Calcium works overtime in the nerve terminal
Cousin, MA
[J]. MOLECULAR NEUROBIOLOGY, 2000, 22 (1-3) : 115 - 128
[5] Protein phosphorylation is required for endocytosis in nerve terminals: potential role for the dephosphins dynamin I and synaptojanin, but not AP180 or amphiphysin
Cousin, MA
Tan, TC
Robinson, PJ
[J]. JOURNAL OF NEUROCHEMISTRY, 2001, 76 (01) : 105 - 116
[6] The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis
Cousin, MA
Robinson, PJ
[J]. TRENDS IN NEUROSCIENCES, 2001, 24 (11) : 659 - 665
[7] COUSIN MA, 2003, J BIOL CHEM 0516
[8] Specificity and mechanism of action of some commonly used protein kinase inhibitors
Davies, SP
Reddy, H
Caivano, M
Cohen, P
[J]. BIOCHEMICAL JOURNAL, 2000, 351 (351) : 95 - 105
[9] A decade of CDK5
Dhavan, R
Tsai, LH
[J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (10) : 749 - 759
[10] Phosphorylation of dynamin by ERK2 inhibits the dynamin-microtubule interaction
Earnest, S
Khokhlatchev, A
Albanesi, JP
Barylko, B
[J]. FEBS LETTERS, 1996, 396 (01) : 62 - 66

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