Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

Yong Kim, Jee Young Sung, Ilaria Ceglia, Ko Woon Lee, Jung Hyuck Ahn, Jonathan M. Halford, Amie M. Kim, Seung P. Kwak, Jong Bae Park, Sung Ho Ryu, Annette Schenck, Barbara Bardoni, John D. Scott, Angus C. Nairn, Paul Greengard

Research output: Contribution to journalArticlepeer-review

257 Scopus citations

Abstract

WAVE1-the Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1-is a key regulator of actin-dependent morphological processes in mammals, through its ability to activate the actin-related protein (Arp2/3) complex. Here we show that WAVE1 is phosphorylated at multiple sites by cyclin-dependent kinase 5 (Cdk5) both in vitro and in intact mouse neurons. Phosphorylation of WAVE1 by Cdk5 inhibits its ability to regulate Arp2/3 complex-dependent actin polymerization. Loss of WAVE1 function in vivo or in cultured neurons results in a decrease in mature dendritic spines. Expression of a dephosphorylation-mimic mutant of WAVE1 reverses this loss of WAVE1 function in spine morphology, but expression of a phosphorylation-mimic mutant does not. Cyclic AMP (cAMP) signalling reduces phosphorylation of the Cdk5 sites in WAVE1, and increases spine density in a WAVE1-dependent manner. Our data suggest that phosphorylation/dephosphorylation of WAVE1 in neurons has an important role in the formation of the filamentous actin cytoskeleton, and thus in the regulation of dendritic spine morphology.

Original languageEnglish
Pages (from-to)814-817
Number of pages4
JournalNature
Volume442
Issue number7104
DOIs
StatePublished - 17 Aug 2006

Bibliographical note

Funding Information:
Acknowledgements We thank W.-B. Gan for assisting us with the DiI staining method; L.-H. Tsai for providing P35 cDNA; A. Yamamoto for Nap1 cDNA; and P. Aspenström for N-WASP antibody. We also thank T. D. Pollard for suggestions. This work was supported by the postdoctoral fellowship programme of the Korea Science & Engineering Foundation (KOSEF) (to J.Y.S.), and funding from the F.M. Kirby foundation (to P.G.), the Picower Foundation (to P.G.), the National Institute of Mental Health, the National Institute of Drug Abuse and the National Institute on Aging (to A.C.N. and P.G.).

Fingerprint

Dive into the research topics of 'Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology'. Together they form a unique fingerprint.

Cite this