Signaltransduction of cytoskeleton and cell movement

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We found N-WASP and WAVE which are involved in actin polymerization at leading edge, and induce filopodia and lamellipodia formation. There are 3 types of WAVE. Among them, WAVE2 is ubiquitously expressed in a wide of tissues and plays crucial role in cell movement at leading edge.We next prepared WAVE1 and 2 knock out mice and established mouse embryonic fibroblasts which do not have WAVE1 or WAVE2. WAVE2-deficient MEF did not induce lamellipodia formation in response to chemoatractants, and speed of cell movement was very slow. On the other hand, WAVE1-deficient MEFdidnot induce dorsal ruffles, though lamellipodia formation was still observed.We also examined whether WAVE is involved in invasion of B16/F10 cells that are high metastatic cell lines. WAVE1 knock down did not affect the cell movement in 3 D collagen. In contrast, WAVE2 knock down inhibited cell movement, invasion in collagen gels. B16/F10 cells of WAVE2 knock down was also suppressed in metastasis to lung.