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Article
Nature Cell Biology  5, 701 - 710 (2003)
Published online: 13 July 2003; | doi:10.1038/ncb1020

Cdk5 is essential for synaptic vesicle endocytosis

Timothy C. Tan1, Valentina A. Valova1, Chandra S. Malladi1, Mark E. Graham1, Leise A. Berven1, Orla J. Jupp6, Gurdip Hansra1, Sonya J. McClure2, Boris Sarcevic3, Ross A. Boadle4, Martin R. Larsen5, Michael A. Cousin6 & Phillip J. Robinson1

1  Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.

2  Royal Hospital for Women in Randwick, Barker St, Randwick, NSW 2031, Australia.

3  Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.

4  Electron Microscope Laboratory, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, 2145, Australia.

5  Australian Proteomic Analysis Facility, Macquarie University, Balaclava Road, North Ryde, NSW 2109, Australia.

6  Membrane Biology Group, Division of Biomedical Sciences, George Square, University of Edinburgh, EH8 9XD, Scotland, UK.

Correspondence should be addressed to Phillip J. Robinson phrobins@mail.usyd.edu.au
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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REFERENCE
Clathrin-coated Vesicles and Receptor-mediated Endocytosis
Nature Encyclopaedia of Life Sciences

REVIEWS
Regulated portals of entry into the cell
Nature Review (06 Mar 2003)
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NEWS AND VIEWS
Cdk5 is a dynamo at the synapse
Nature Cell Biology News and Views (01 Aug 2003)
Cell biology: Lipid membranes shape up
Nature News and Views (09 Sep 1999)

RESEARCH
Calcium accelerates endocytosis of vSNAREs at hippocampal synapses
Nature Neuroscience Article (01 Feb 2001)
 See all 2 matches for Research

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Nature Cell Biology
ISSN: 1465-7392
EISSN: 1476-4679
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