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PMID: 12855954 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cdk5 is essential for synaptic vesicle endocytosis.

Nature cell biology ·Vol. 5 ·No. 8 ·2003-08-00 ·Pages 701-10

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

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.

MeSH Terms

Amino Acid Motifs Animals Cyclin-Dependent Kinase 5 Cyclin-Dependent Kinases/chemistry,genetics,metabolism Dynamin I/genetics,metabolism Endocytosis/physiology Enzyme Inhibitors/metabolism Monomeric Clathrin Assembly Proteins/metabolism Nerve Tissue Proteins/genetics,metabolism Neurons/cytology,metabolism Peptides/chemistry,metabolism Phosphorylation Protein Kinase C/metabolism Protein Kinase C-alpha Purines/metabolism Rats Recombinant Fusion Proteins/metabolism Roscovitine Serine/metabolism Sheep Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Synapses/metabolism Synaptic Vesicles/metabolism Synaptosomes/chemistry,metabolism,ultrastructure

Chemicals

Enzyme Inhibitors Monomeric Clathrin Assembly Proteins Nerve Tissue Proteins Peptides Purines Recombinant Fusion Proteins clathrin assembly protein AP180 Roscovitine amphiphysin Serine Cyclin-Dependent Kinase 5 Protein Kinase C Protein Kinase C-alpha Cdk5 protein, rat Cyclin-Dependent Kinases Dynamin I

Authors & Affiliations

13 authors, click to expand affiliations / ORCID

Tan Timothy C

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

Valova Valentina A

Malladi Chandra S

Graham Mark E

Berven Leise A

Jupp Orla J

Hansra Gurdip

McClure Sonya J

Sarcevic Boris

Boadle Ross A

Larsen Martin R

Cousin Michael A

Robinson Phillip J

Article Info

Journal

Nature cell biology

Abbr.

Nat Cell Biol

ISSN

1465-7392

DOI

10.1038/ncb1020

Published

2003-08-00

Pages

701-10

Language

English

Region

England

NLM ID

100890575

Subset

Corrections

CommentIn

PMID: 12894171

External Links

PubMed source DOI: 10.1038/ncb1020 View journal details

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