title: crossveinless-c is a RhoGAP required for actin reorganisation during morphogenesis.
abstract: Members of the Rho family of small GTPases are required for many of the morphogenetic processes required to shape the animal body. The activity of this family is regulated in part by a class of proteins known as RhoGTPase Activating Proteins (RhoGAPs) that catalyse the conversion of RhoGTPases to their inactive state. In our search for genes that regulate Drosophila morphogenesis, we have isolated several lethal alleles of crossveinless-c (cv-c). Molecular characterisation reveals that cv-c encodes the RhoGAP protein RhoGAP88C. During embryonic development, cv-c is expressed in tissues undergoing morphogenetic movements; phenotypic analysis of the mutants reveals defects in the morphogenesis of these tissues. Genetic interactions between cv-c and RhoGTPase mutants indicate that Rho1, Rac1 and Rac2 are substrates for Cv-c, and suggest that the substrate specificity might be regulated in a tissue-dependent manner. In the absence of cv-c activity, tubulogenesis in the renal or Malpighian tubules fails and they collapse into a cyst-like sack. Further analysis of the role of cv-c in the Malpighian tubules demonstrates that its activity is required to regulate the reorganisation of the actin cytoskeleton during the process of convergent extension. In addition, overexpression of cv-c in the developing tubules gives rise to actin-associated membrane extensions. Thus, Cv-c function is required in tissues actively undergoing morphogenesis, and we propose that its role is to regulate RhoGTPase activity to promote the coordinated organisation of the actin cytoskeleton, possibly by stabilising plasma membrane/actin cytoskeleton interactions.
authors.affiliation: Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Denholm
authors.forename: Stephen
authors.initials: S
authors.lastname: Brown
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ray
authors.forename: Mar
authors.initials: M
authors.lastname: Ruiz-Gómez
authors.forename: Helen
authors.initials: H
authors.lastname: Skaer
authors.forename: James Castelli-Gair
authors.initials: JC
authors.lastname: Hombría
mesh_terms: D000199:Actins / Q000378:metabolism*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D040461:Gene Components; D007150:Immunohistochemistry; D008317:Malpighian Tubules / Q000196:embryology*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016296:Mutagenesis; D020641:Polymorphism, Single Nucleotide; D013379:Substrate Specificity; D014921:Wings, Animal / Q000033:anatomy & histology; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C502709:cv-c protein, Drosophila; C511153:Rho1 protein, Drosophila