Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

• Published in: Nature 2006-08, Vol.442 (7104), p.814-817
• Main Authors: Ceglia, Ilaria, Kwak, Seung P, Bardoni, Barbara, Ho Ryu, Sung, Greengard, Paul, Sung, Jee Young, Kim, Amie M, Kim, Yong, Scott, John D, Lee, Ko-Woon, Halford, Jonathan M, Park, Jong Bae, Schenck, Annette, Nairn, Angus C, Ahn, Jung-Hyuck
• Format: Article
• Language: English
• Subjects: Actins - chemistry; Actins - metabolism; Animals; Biochemistry, Molecular Biology; Biological and medical sciences; Biopolymers - metabolism; Cells, Cultured; Cyclic AMP - metabolism; Cyclin-Dependent Kinase 5 - metabolism; Cyclin-dependent kinases; Cytoskeleton - chemistry; Cytoskeleton - metabolism; Dendrites - metabolism; Dendrites - physiology; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Isolated neuron and nerve. Neuroglia; Kinases; letter; Life Sciences; Male; Mammals; Mice; Mice, Inbred C57BL; Morphology; multidisciplinary; Mutants; Mutation; Neurons; Phosphorylation; Polymerization; Proteins; Rabbits; Science; Science (multidisciplinary); Vertebrates: nervous system and sense organs; Wiskott-Aldrich Syndrome Protein Family - metabolism
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature04976

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.