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

TY - JOUR

T1 - Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

AU - Law, Ah-Lai

AU - Vehlow, Anne

AU - Kotini, Maria

AU - Dodgson, Lauren

AU - Soong, Daniel

AU - Theveneau, Eric

AU - Bodo, Cristian

AU - Taylor, Eleanor

AU - Navarro, Christel

AU - Perera, Upamali

AU - Michael, Magdalene

AU - Dunn, Graham

AU - Bennett, Daimark

AU - Mayor, Roberto

AU - Krause, Matthias

PY - 2013/11

Y1 - 2013/11

N2 - 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 via the Scar/WAVE complex. Further, Lpd’s Drosophila 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.

AB - 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 via the Scar/WAVE complex. Further, Lpd’s Drosophila 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.

U2 - 10.1083/jcb.201304051

DO - 10.1083/jcb.201304051

M3 - Article

SN - 0021-9525

VL - 203

SP - 673

EP - 689

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 4

M1 - N/A

ER -