title: Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo.
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.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, and 2 British Heart Foundation Centre of Excellence, James Black Centre, Cardiovascular Division, King's College London, London SE1 1UL, England, UK.
authors.forename: Ah-Lai
authors.initials: AL
authors.lastname: Law
authors.forename: Anne
authors.initials: A
authors.lastname: Vehlow
authors.forename: Maria
authors.initials: M
authors.lastname: Kotini
authors.forename: Lauren
authors.initials: L
authors.lastname: Dodgson
authors.forename: Daniel
authors.initials: D
authors.lastname: Soong
authors.forename: Eric
authors.initials: E
authors.lastname: Theveneau
authors.forename: Cristian
authors.initials: C
authors.lastname: Bodo
authors.forename: Eleanor
authors.initials: E
authors.lastname: Taylor
authors.forename: Christel
authors.initials: C
authors.lastname: Navarro
authors.forename: Upamali
authors.initials: U
authors.lastname: Perera
authors.forename: Magdalene
authors.initials: M
authors.lastname: Michael
authors.forename: Graham A
authors.initials: GA
authors.lastname: Dunn
authors.forename: Daimark
authors.initials: D
authors.lastname: Bennett
authors.forename: Roberto
authors.initials: R
authors.lastname: Mayor
authors.forename: Matthias
authors.initials: M
authors.lastname: Krause
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D010858:Pigmentation; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D018909:src Homology Domains
chemical_list: C513734:Abi1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; C533183:Pico protein, Drosophila; D051300:Wiskott-Aldrich Syndrome Protein Family; D049452:Green Fluorescent Proteins; D020744:rac GTP-Binding Proteins