Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

作者:Law Ah Lai; Vehlow Anne; Kotini Maria; Dodgson Lauren; Soong Daniel; Theveneau Eric; Bodo Cristian; Taylor Eleanor; Navarro Christel; Perera Upamali; Michael Magdalene; Dunn Graham A; Bennett Daimark; Mayor Roberto; Krause Matthias*
来源:The Journal of Cell Biology, 2013, 203(4): 673-689.
DOI:10.1083/jcb.201304051

摘要

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%26apos;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.

  • 出版日期2013-11-25