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First published online 27 November 2007
doi: 10.1242/jcs.018218

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.018218v1 120/24/4355    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miyamoto, Y. Articles by Tanoue, A. Search for Related Content PubMed PubMed Citation Articles by Miyamoto, Y. Articles by Tanoue, A.

Cdk5 regulates differentiation of oligodendrocyte precursor cells through the direct phosphorylation of paxillin

¹ Department of Pharmacology, National Research Institute for Child Health and Development, Okura, Setagaya, Tokyo 157-8535, Japan
² Department of Cell and Neurobiology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
³ Department of Biological Science and Technology, and Tissue Research Center, Tokyo University of Science, Yamazaki, Noda City, Chiba 278-8510, Japan
⁴ Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Minami-Osawa, Hachiohji City, Tokyo 194-8511, Japan

^* Author for correspondence (e-mail: jyamauchi{at}nch.go.jp)

Accepted 6 October 2007

Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs) in order to form myelin, which is required for the rapid propagation of action potentials in the vertebrate nervous system. In spite of the considerable clinical importance of myelination, little is known about the basic molecular mechanisms underlying OL differentiation and myelination. Here, we show that cyclin-dependent kinase (Cdk) 5 is activated following the induction of differentiation, and that the Cdk5 inhibitor roscovitine inhibits OL differentiation. The complexity of the OL processes is also diminished after knocking down endogenous Cdk5 using RNAi. We also show that the focal adhesion protein paxillin is directly phosphorylated at Ser244 by Cdk5. Transfection of a paxillin construct harboring a Ser244 to Ala mutation dramatically inhibits its morphological effects. Importantly, phosphorylation of paxillin at Ser244 reduces its interaction with focal adhesion kinase (FAK). Taken together, these results suggest that phosphorylation of paxillin by Cdk5 is a key mechanism in OL differentiation and may ultimately regulate myelination.

Key words: Cdk5, Paxillin, Ser phosphorylation, Differentiation, Oligodendrocyte precursor cells, CNS

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