title: Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology.
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.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Sung
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ceglia
authors.forename: Ko-Woon
authors.initials: KW
authors.lastname: Lee
authors.forename: Jung-Hyuck
authors.initials: JH
authors.lastname: Ahn
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Halford
authors.forename: Amie M
authors.initials: AM
authors.lastname: Kim
authors.forename: Seung P
authors.initials: SP
authors.lastname: Kwak
authors.forename: Jong Bae
authors.initials: JB
authors.lastname: Park
authors.forename: Sung
authors.initials: S
authors.lastname: Ho Ryu
authors.forename: Annette
authors.initials: A
authors.lastname: Schenck
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
authors.forename: John D
authors.initials: JD
authors.lastname: Scott
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001704:Biopolymers / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011817:Rabbits; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
chemical_list: D000199:Actins; D001704:Biopolymers; D051300:Wiskott-Aldrich Syndrome Protein Family; D000242:Cyclic AMP; D051360:Cyclin-Dependent Kinase 5