期刊
NATURE
卷 442, 期 7104, 页码 814-817出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature04976
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资金
- NIDA NIH HHS [P01 DA010044] Funding Source: Medline
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.
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