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- Title
Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology.
- Authors
Yong Kim; Jee Young Sung; Ceglia, Ilaria; Ko-Woon Lee; Jung-Hyuck Ahn; Halford, Jonathan M.; Kim, Amie M.; Kwak, Seung P.; Jong Bae Park; Sung Ho Ryu; Schenck, Annette; Bardoni, Barbara; Scott, John D.; Nairn, Angus C.; Greengard, Paul
- 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.
- Publication
Nature, 2006, Vol 442, Issue 7104, p814
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature04976