WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility

被引:150
作者
Yan, C
Martinez-Quiles, N
Eden, S
Shibata, T
Takeshima, F
Shinkura, R
Fujiwara, Y
Bronson, R
Snapper, SB
Kirschner, MW
Geha, R
Rosen, FS
Alt, FW
机构
[1] Ctr Blood Res, Boston, MA 02115 USA
[2] Howard Hughes Med Inst, Div Immunol, Boston, MA 02115 USA
[3] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[8] Massachusetts Gen Hosp, Gastrointestinal Unit Med Serv, Boston, MA 02115 USA
[9] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA
关键词
actin polymerization; lamellipodium; Rho GTPase; WASP-related protein; WAVE;
D O I
10.1093/emboj/cdg350
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Wiskott-Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement.
引用
收藏
页码:3602 / 3612
页数:11
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