Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology
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SCOPUS
- Title
- Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology
- Authors
- Kim, Y; Sung, JY; Ceglia, I; Lee, KW; Ahn, JH; Halford, JM; Kim, AM; Kwak, SP; Park, JB; Ryu, SH; Schenck, A; Bardoni, B; Scott, JD; Nairn, AC; Greengard, P
- Date Issued
- 2006-08-17
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- WAVE1 - the Wiskott - Aldrich syndrome protein ( WASP)- family verprolin homologous protein 1 - is a key regulator of actin-dependent morphological processes(1) 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.
- Keywords
- CYCLIN-DEPENDENT KINASE-5; NUCLEUS-ACCUMBENS; FAMILY PROTEINS; ARP2/3 COMPLEX; SMALL GTPASES; CDK5; WASP; DOPAMINE; NEURONS; COCAINE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/23867
- DOI
- 10.1038/NATURE04976
- ISSN
- 0028-0836
- Article Type
- Article
- Citation
- NATURE, vol. 442, no. 7104, page. 814 - 817, 2006-08-17
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