Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

Yong Kim; Jee Young Sung; Ilaria Ceglia; Ko Woon Lee; Jung Hyuck Ahn; Jonathan M. Halford; Amie M. Kim; Seung P. Kwak; Jong Bae Park; Sung Ho Ryu; Annette Schenck; Barbara Bardoni; John D. Scott; Angus C. Nairn; Paul Greengard

doi:10.1038/nature04976

Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

Yong Kim, Jee Young Sung, Ilaria Ceglia, Ko Woon Lee, Jung Hyuck Ahn, Jonathan M. Halford, Amie M. Kim, Seung P. Kwak, Jong Bae Park, Sung Ho Ryu, Annette Schenck, Barbara Bardoni, John D. Scott, Angus C. Nairn, Paul Greengard

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

262 Scopus citations

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.

Original language	English
Pages (from-to)	814-817
Number of pages	4
Journal	Nature
Volume	442
Issue number	7104
DOIs	https://doi.org/10.1038/nature04976
State	Published - 17 Aug 2006

Bibliographical note

Funding Information:
Acknowledgements We thank W.-B. Gan for assisting us with the DiI staining method; L.-H. Tsai for providing P35 cDNA; A. Yamamoto for Nap1 cDNA; and P. Aspenström for N-WASP antibody. We also thank T. D. Pollard for suggestions. This work was supported by the postdoctoral fellowship programme of the Korea Science & Engineering Foundation (KOSEF) (to J.Y.S.), and funding from the F.M. Kirby foundation (to P.G.), the Picower Foundation (to P.G.), the National Institute of Mental Health, the National Institute of Drug Abuse and the National Institute on Aging (to A.C.N. and P.G.).

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@article{384170219db84b1b82df3f269361828c,

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.",

author = "Yong Kim and Sung, {Jee Young} and Ilaria Ceglia and Lee, {Ko Woon} and Ahn, {Jung Hyuck} and Halford, {Jonathan M.} and Kim, {Amie M.} and Kwak, {Seung P.} and Park, {Jong Bae} and {Ho Ryu}, Sung and Annette Schenck and Barbara Bardoni and Scott, {John D.} and Nairn, {Angus C.} and Paul Greengard",

note = "Funding Information: Acknowledgements We thank W.-B. Gan for assisting us with the DiI staining method; L.-H. Tsai for providing P35 cDNA; A. Yamamoto for Nap1 cDNA; and P. Aspenstr{\"o}m for N-WASP antibody. We also thank T. D. Pollard for suggestions. This work was supported by the postdoctoral fellowship programme of the Korea Science & Engineering Foundation (KOSEF) (to J.Y.S.), and funding from the F.M. Kirby foundation (to P.G.), the Picower Foundation (to P.G.), the National Institute of Mental Health, the National Institute of Drug Abuse and the National Institute on Aging (to A.C.N. and P.G.).",

year = "2006",

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doi = "10.1038/nature04976",

language = "English",

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T1 - Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

AU - Kim, Yong

AU - Sung, Jee Young

AU - Ceglia, Ilaria

AU - Lee, Ko Woon

AU - Ahn, Jung Hyuck

AU - Halford, Jonathan M.

AU - Kim, Amie M.

AU - Kwak, Seung P.

AU - Park, Jong Bae

AU - Ho Ryu, Sung

AU - Schenck, Annette

AU - Bardoni, Barbara

AU - Scott, John D.

AU - Nairn, Angus C.

AU - Greengard, Paul

N1 - Funding Information: Acknowledgements We thank W.-B. Gan for assisting us with the DiI staining method; L.-H. Tsai for providing P35 cDNA; A. Yamamoto for Nap1 cDNA; and P. Aspenström for N-WASP antibody. We also thank T. D. Pollard for suggestions. This work was supported by the postdoctoral fellowship programme of the Korea Science & Engineering Foundation (KOSEF) (to J.Y.S.), and funding from the F.M. Kirby foundation (to P.G.), the Picower Foundation (to P.G.), the National Institute of Mental Health, the National Institute of Drug Abuse and the National Institute on Aging (to A.C.N. and P.G.).

PY - 2006/8/17

Y1 - 2006/8/17

N2 - 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.

AB - 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.

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U2 - 10.1038/nature04976

DO - 10.1038/nature04976

M3 - Article

C2 - 16862120

AN - SCOPUS:33747482904

SN - 0028-0836

VL - 442

SP - 814

EP - 817

JO - Nature

JF - Nature

IS - 7104

ER -

Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology

Abstract

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