Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration
Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration
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DOI：
10.1016/s1534-5807(03)00297-1
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发表时间：
2003-10-01
影响因子：
11.8
通讯作者：
Takenawa, T
中科院分区：
文献类型：
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作者：
Suetsugu, S;Yamazaki, D;Takenawa, T
细胞迁移是由片状伪足前缘的肌动蛋白聚合驱动的，其中WASP家族的verprolin同源蛋白（WAVE）激活Arp 2/3复合物。当用PDGF刺激成纤维细胞时，在板状伪足中外周皱褶的形成先于背侧皱褶的形成。在这里，我们表明，WAVE 2缺陷损害外周皱褶的形成和WAVE 1缺陷损害背皱褶的形成。在不存在细胞外基质（ECM）的情况下定向细胞迁移期间，细胞在前缘处以外周皱褶迁移，并且WAVE 2而不是WAVE 1是必需的。相反，WAVE 1和WAVE 2都是入侵迁移到ECM中所必需的，这表明ECM中的前缘具有两种皱褶的特征。WAVE 1与背褶中的ECM降解酶MMP-2共定位，并且WAVE 1依赖性迁移（而不是WAVE 2依赖性迁移）需要MMP活性。因此，WAVE 2通常对于定向迁移的前缘延伸是必不可少的，WAVE 1在ECM中MMP依赖性迁移中是必不可少的。
Cell migration is driven by actin polymerization at the leading edge of lamellipodia, where WASP family verprolin-homologous proteins (WAVEs) activate Arp2/3 complex. When fibroblasts are stimulated with PDGF, formation of peripheral ruffles precedes that of dorsal ruffles in lamellipodia. Here, we show that WAVE2 deficiency impairs peripheral ruffle formation and WAVE1 deficiency impairs dorsal ruffle formation. During directed cell migration in the absence of extracellular matrix (ECM), cells migrate with peripheral ruffles at the leading edge and WAVE2, but not WAVE1, is essential. In contrast, both WAVE1 and WAVE2 are essential for invading migration into ECM, suggesting that the leading edge in ECM has characteristics of both ruffles. WAVE1 is colocalized with ECM-degrading enzyme MMP-2 in dorsal ruffles, and WAVE1-, but not WAVE2-, dependent migration requires MMP activity. Thus, WAVE2 is essential for leading edge extension for directed migration in general and WAVE1 is essential in MMP-dependent migration in ECM.