title: Regulation of Rho and Rac signaling to the actin cytoskeleton by paxillin during Drosophila development.
abstract: Paxillin is a prominent focal adhesion docking protein that regulates cell adhesion and migration. Although numerous paxillin-binding proteins have been identified and paxillin is required for normal embryogenesis, the precise mechanism by which paxillin functions in vivo has not yet been determined. We identified an ortholog of mammalian paxillin in Drosophila (Dpax) and have undertaken a genetic analysis of paxillin function during development. Overexpression of Dpax disrupted leg and wing development, suggesting a role for paxillin in imaginal disc morphogenesis. These defects may reflect a function for paxillin in regulation of Rho family GTPase signaling as paxillin interacts genetically with Rac and Rho in the developing eye. Moreover, a gain-of-function suppressor screen identified a genetic interaction between Dpax and cdi in wing development. cdi belongs to the cofilin kinase family, which includes the downstream Rho target, LIM kinase (LIMK). Significantly, strong genetic interactions were detected between Dpax and Dlimk, as well as downstream effectors of Dlimk. Supporting these genetic data, biochemical studies indicate that paxillin regulates Rac and Rho activity, positively regulating Rac and negatively regulating Rho. Taken together, these data indicate the importance of paxillin modulation of Rho family GTPases during development and identify the LIMK pathway as a critical target of paxillin-mediated Rho regulation.
authors.affiliation: Massachusetts General Hospital Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Guang-Chao
authors.initials: GC
authors.lastname: Chen
authors.forename: Brian
authors.initials: B
authors.lastname: Turano
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Ruest
authors.forename: Margit
authors.initials: M
authors.lastname: Hagel
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Settleman
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Thomas
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D054461:Lim Kinases; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D051419:Paxillin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014921:Wings, Animal / Q000254:growth & development; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C496059:Pax protein, Drosophila; D051419:Paxillin; D010750:Phosphoproteins; D011494:Protein Kinases; D054461:Lim Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins