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XB-ART-47766
J Cell Biol November 25, 2013; 203 (4): 673-89.

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

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 .


Abstract
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.

PubMed ID: 24247431
PMC ID: PMC3840943
Article link: J Cell Biol
Grant support: [+]
Genes referenced: abi1 actl6a actr3 cyfip1 dct fn1 gnl3 hspa8 lgals4.2 mbp myc npat rac1 scaf1 sox9 sra1 tab3 tbx2 twist1 wasf1 wasf2


Article Images: [+] show captions
References:
Bear, 2002, Pubmed [+]


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