WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility
WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility
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DOI：
10.1093/emboj/cdg350
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发表时间：
2003-07-15
期刊：
影响因子：
11.4
通讯作者：
Alt, FW
中科院分区：
文献类型：
--
作者：
Yan, C;Martinez-Quiles, N;Alt, FW
Wiskott-Aldrich综合征相关蛋白WAVE2参与了小Rho GTPase Rac下游肌动蛋白-细胞骨架重组的调控。我们通过基因靶向突变使WAVE2基因失活，以检测它在小鼠发育和肌动蛋白组装中的作用。WAVE2基因缺陷的胚胎存活到胚胎12.5天左右，表现出生长迟缓和某些形态缺陷，包括发育中的脑室畸形。WAVE2缺陷的胚胎干细胞表现出正常的增殖，而WAVE2缺陷的胚胎成纤维细胞表现出严重的生长缺陷，以及细胞在PDGF、片层形成和RAC介导的肌动蛋白聚合反应中的运动缺陷。这些结果暗示了WAVE2在小鼠胚胎发育中的非多余作用，以及WAVE2在RAC下游基于肌动蛋白的过程中的关键作用，而RAC下游的肌动蛋白对细胞运动至关重要。
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.