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Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo
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...
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| Published in: | The Journal of cell biology 2013-11, Vol.203 (4), p.673-689 |
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| creator | Law, Ah-Lai Vehlow, Anne Kotini, Maria Dodgson, Lauren Soong, Daniel Theveneau, Eric Bodo, Cristian Taylor, Eleanor Navarro, Christel Perera, Upamali Michael, Magdalene Dunn, Graham A Bennett, Daimark Mayor, Roberto Krause, Matthias |
| description | 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. |
| doi_str_mv | 10.1083/jcb.201304051 |
| format | article |
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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.</description><identifier>ISSN: 0021-9525</identifier><identifier>ISSN: 1540-8140</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.201304051</identifier><identifier>PMID: 24247431</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Adaptor Proteins, Signal Transducing - chemistry ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Binding Sites ; Cell Movement ; Cellular biology ; Cytoskeletal Proteins - chemistry ; Cytoskeletal Proteins - metabolism ; Drosophila melanogaster - cytology ; Drosophila melanogaster - metabolism ; Drosophila Proteins - metabolism ; Epithelial Cells - cytology ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Green Fluorescent Proteins - metabolism ; HEK293 Cells ; Humans ; Insects ; Life Sciences ; Melanocytes - cytology ; Melanocytes - metabolism ; Melanoma, Experimental - metabolism ; Melanoma, Experimental - pathology ; Membrane Proteins - metabolism ; Metastasis ; Mice ; Mice, Knockout ; Neural Crest - cytology ; Neural Crest - metabolism ; NIH 3T3 Cells ; Pigmentation ; Protein Binding ; Proteins ; Pseudopodia - metabolism ; rac GTP-Binding Proteins - metabolism ; Rodents ; src Homology Domains ; Wiskott-Aldrich Syndrome Protein Family - metabolism ; Xenopus - metabolism</subject><ispartof>The Journal of cell biology, 2013-11, Vol.203 (4), p.673-689</ispartof><rights>Copyright Rockefeller University Press Nov 25, 2013</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2013 Law et al. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-255df0b81c48da55161cd0c899cac0a0b968a54de2e8f9d3474296250d1a60b73</citedby><cites>FETCH-LOGICAL-c515t-255df0b81c48da55161cd0c899cac0a0b968a54de2e8f9d3474296250d1a60b73</cites><orcidid>0000-0001-6510-5717</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24247431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04727632$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Law, Ah-Lai</creatorcontrib><creatorcontrib>Vehlow, Anne</creatorcontrib><creatorcontrib>Kotini, Maria</creatorcontrib><creatorcontrib>Dodgson, Lauren</creatorcontrib><creatorcontrib>Soong, Daniel</creatorcontrib><creatorcontrib>Theveneau, Eric</creatorcontrib><creatorcontrib>Bodo, Cristian</creatorcontrib><creatorcontrib>Taylor, Eleanor</creatorcontrib><creatorcontrib>Navarro, Christel</creatorcontrib><creatorcontrib>Perera, Upamali</creatorcontrib><creatorcontrib>Michael, Magdalene</creatorcontrib><creatorcontrib>Dunn, Graham A</creatorcontrib><creatorcontrib>Bennett, Daimark</creatorcontrib><creatorcontrib>Mayor, Roberto</creatorcontrib><creatorcontrib>Krause, Matthias</creatorcontrib><title>Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>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.</description><subject>Adaptor Proteins, Signal Transducing - chemistry</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Cell Movement</subject><subject>Cellular biology</subject><subject>Cytoskeletal Proteins - chemistry</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Drosophila melanogaster - cytology</subject><subject>Drosophila melanogaster - metabolism</subject><subject>Drosophila Proteins - metabolism</subject><subject>Epithelial Cells - cytology</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Insects</subject><subject>Life Sciences</subject><subject>Melanocytes - cytology</subject><subject>Melanocytes - 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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.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>24247431</pmid><doi>10.1083/jcb.201304051</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-6510-5717</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - chemistry Adaptor Proteins, Signal Transducing - metabolism Animals Binding Sites Cell Movement Cellular biology Cytoskeletal Proteins - chemistry Cytoskeletal Proteins - metabolism Drosophila melanogaster - cytology Drosophila melanogaster - metabolism Drosophila Proteins - metabolism Epithelial Cells - cytology Fibroblasts - cytology Fibroblasts - metabolism Green Fluorescent Proteins - metabolism HEK293 Cells Humans Insects Life Sciences Melanocytes - cytology Melanocytes - metabolism Melanoma, Experimental - metabolism Melanoma, Experimental - pathology Membrane Proteins - metabolism Metastasis Mice Mice, Knockout Neural Crest - cytology Neural Crest - metabolism NIH 3T3 Cells Pigmentation Protein Binding Proteins Pseudopodia - metabolism rac GTP-Binding Proteins - metabolism Rodents src Homology Domains Wiskott-Aldrich Syndrome Protein Family - metabolism Xenopus - metabolism |
| title | Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo |
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