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

240 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

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