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PMID:12853475

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Citation

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 and Alt, FW (2003) WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. EMBO J. 22:3602-12

Abstract

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.

Links

PubMed PMC165620 Online version:10.1093/emboj/cdg350

Keywords

Actins/metabolism; Actins/physiology; Animals; Biopolymers; Cell Line; Cell Movement/physiology; Cytoskeleton/metabolism; Embryo, Mammalian/cytology; Embryo, Mammalian/physiology; Fibroblasts/cytology; Fibroblasts/metabolism; Gene Deletion; Mice; Mice, Knockout; Microfilament Proteins/deficiency; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Mutation; Protein Isoforms/deficiency; Protein Isoforms/genetics; Protein Isoforms/metabolism; Pseudopodia/metabolism; RNA/metabolism; Stem Cells/cytology; Stem Cells/metabolism; Wiskott-Aldrich Syndrome/blood; Wiskott-Aldrich Syndrome/metabolism; Wiskott-Aldrich Syndrome Protein Family; rac GTP-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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