Cdk5 is essential for synaptic vesicle endocytosis

Timothy C. Tan; Valentina A. Valova; Chandra S. Malladi; Mark E. Graham; Leise A. Berven; Orla J. Jupp; Gurdip Hansra; Sonya J. McClure; Boris Sarcevic; Ross Boadle; Martin R. Larsen; Michael A. Cousin; Phillip J. Robinson

doi:10.1038/ncb1020

Cdk5 is essential for synaptic vesicle endocytosis

Timothy C. Tan, Valentina A. Valova, Chandra S. Malladi, Mark E. Graham, Leise A. Berven, Orla J. Jupp, Gurdip Hansra, Sonya J. McClure, Boris Sarcevic, Ross Boadle, Martin R. Larsen, Michael A. Cousin, Phillip J. Robinson

Research output: Contribution to journal › Article › peer-review

267 Citations (Scopus)

Abstract

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 I, 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.

Original language	English
Pages (from-to)	701-710
Number of pages	10
Journal	Nature Cell Biology
Volume	5
Issue number	8
DOIs	https://doi.org/10.1038/ncb1020
Publication status	Published - 1 Aug 2003
Externally published	Yes

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title = "Cdk5 is essential for synaptic vesicle endocytosis",

abstract = "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 I, 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.",

author = "Tan, {Timothy C.} and Valova, {Valentina A.} and Malladi, {Chandra S.} and Graham, {Mark E.} and Berven, {Leise A.} and Jupp, {Orla J.} and Gurdip Hansra and McClure, {Sonya J.} and Boris Sarcevic and Ross Boadle and Larsen, {Martin R.} and Cousin, {Michael A.} and Robinson, {Phillip J.}",

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T1 - Cdk5 is essential for synaptic vesicle endocytosis

AU - Tan, Timothy C.

AU - Valova, Valentina A.

AU - Malladi, Chandra S.

AU - Graham, Mark E.

AU - Berven, Leise A.

AU - Jupp, Orla J.

AU - Hansra, Gurdip

AU - McClure, Sonya J.

AU - Sarcevic, Boris

AU - Boadle, Ross

AU - Larsen, Martin R.

AU - Cousin, Michael A.

AU - Robinson, Phillip J.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - 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 I, 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.

AB - 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 I, 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.

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Cdk5 is essential for synaptic vesicle endocytosis

Abstract

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