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

Research output: Contribution to journalArticle

Ah-Lai Law, Anne Vehlow, Maria Kotini, Lauren Dodgson, Daniel Soong, Eric Theveneau, Cristian Bodo, Eleanor Taylor, Christel Navarro, Upamali Perera, Magdalene Michael, Graham Dunn, Daimark Bennett, Roberto Mayor, Matthias Krause

Original languageEnglish
Article numberN/A
Pages (from-to)673-689
Number of pages23
JournalJournal of Cell Biology
Volume203
Issue number4
Early online date18 Nov 2013
DOIs
Publication statusPublished - Nov 2013

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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 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.

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