Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo.
Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo.
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DOI：
10.1083/jcb.201304051
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发表时间：
2013-11-25
期刊：
影响因子：
--
通讯作者：
Krause M
中科院分区：
文献类型：
--
作者：
Law AL;Vehlow A;Kotini M;Dodgson L;Soong D;Theveneau E;Bodo C;Taylor E;Navarro C;Perera U;Michael M;Dunn GA;Bennett D;Mayor R;Krause M
LPD是体内细胞迁移过程中SCAR/WAVE复合体的一个必不可少的、进化保守的调节因子。细胞迁移对发育是必不可少的，但它的放松调控会导致转移。SCAR/WAVE复合体是片状脂溢症所必需的，是细胞迁移的关键效应器，但其在体内的调控仍是一个谜。片状脂蛋白(LPD)通过一种未知的机制控制片状脂膜的形成。在这里，我们报道了LPD直接与活性RAC结合，活性RAC通过Abi调节LPD与SCAR/WAVE复合体之间的直接相互作用。因此，LPD在体外通过SCAR/WAVE控制片层的大小、细胞迁移速度和持久性。此外，LPD基因敲除小鼠表现出有缺陷的色素沉着，因为在发育过程中较少迁移的神经脊源性黑素母细胞到达它们的目标。在非洲爪哇，LPD通过SCAR/WAVE复合体自主地调节间充质神经脊细胞的迁移。此外，LPD的果蝇黑腹直系物Pico结合SCAR，两者都调节集体上皮边缘细胞的迁移。Pico还以一种依赖疤痕的方式控制边缘细胞团的定向细胞突起。综上所述，LPD是体内细胞迁移过程中SCAR/WAVE复合体的一个必不可少的、进化保守的调节因子。
Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo. Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16.2
作者：
Lanier, LM;Gates, MA;Gertler, FB
通讯作者：
Gertler, FB
影响因子：
11.8
作者：
Lyulcheva, Ekaterina;Taylor, Eleanor;Michael, Magdalene;Vehlow, Anne;Tan, Shengjiang;Fletcher, Adam;Krause, Matthias;Bennett, Daimark
通讯作者：
Bennett, Daimark
影响因子：
64.5
作者：
Bear, JE;Loureiro, JJ;Gertler, FB
通讯作者：
Gertler, FB
影响因子：
3.5
作者：
Hahne, P;Sechi, A;Small, JV
通讯作者：
Small, JV