Crossveinless-c is a RhoGAP required for actin reorganisation during morphogenesis

Denholm, B, Brown, S, Ray, R P, Ruiz-Gómez, M, Skaer, H and Hombría, J C (2005) Crossveinless-c is a RhoGAP required for actin reorganisation during morphogenesis. Development, 132 (10). pp. 2389-2400. ISSN 0950-1991

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embers 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

Item Type: Article
Additional Information: Collaboration with Dr. Skaer and Dr. Castelli-Gair, this article presents the first phenotypic analysis of mutations in a RhoGAP, and shows that cv-c is required for actin reorganization during morphogenesis. Dr. Ray's contribution included genetic screens for alleles, phenotypic analysis in the wing, and molecular characterization of the locus.
Schools and Departments: School of Life Sciences > Evolution, Behaviour and Environment
Depositing User: Robert Ray
Date Deposited: 06 Feb 2012 20:20
Last Modified: 30 Nov 2012 17:06
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