Journal
JOURNAL OF CELL BIOLOGY
Volume 203, Issue 4, Pages 673-689Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201304051
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Funding
- Medical Research Council Capacity Building studentship
- British Heart Foundation [RE/08/003]
- Latsis Public Benefit Foundation
- Wellcome Trust Value in People award
- Medical Research Council studentship
- European Molecular Biology Organization long-term fellowship
- Cancer Research UK [C20691/A11834, C20691/A6678]
- North West Cancer Research [CR847]
- Wellcome Trust [084659/Z/08/Z, 077429/Z/05/Z, 082907/Z/07/Z]
- Medical Research Council UK [MR/J000655/1]
- Biotechnology and Biological Sciences Research Council [BB/G00319X/1, BB/F011431/1, BB/J000590/1]
- BBSRC [BB/J000590/1, BB/F011431/1, BB/G00319X/1] Funding Source: UKRI
- MRC [MR/J000655/1, G0401026] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/G00319X/1, BB/F011431/1, BB/J000590/1] Funding Source: researchfish
- Medical Research Council [MR/J000655/1] Funding Source: researchfish
- Wellcome Trust [084659/Z/08/Z, 082907/Z/07/Z] Funding Source: Wellcome Trust
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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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