Article abstract
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
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.
- Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.
- Royal Hospital for Women in Randwick, Barker St, Randwick, NSW 2031, Australia.
- Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
- Electron Microscope Laboratory, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, 2145, Australia.
- Australian Proteomic Analysis Facility, Macquarie University, Balaclava Road, North Ryde, NSW 2109, Australia.
- Membrane Biology Group, Division of Biomedical Sciences, George Square, University of Edinburgh, EH8 9XD, Scotland, UK.
Correspondence to: Phillip J. Robinson1 e-mail: phrobins@mail.usyd.edu.au
|
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REFERENCE REVIEWS NEWS AND VIEWS RESEARCH |
