Abstract
C3G is a guanine nucleotide exchange factor (GEF) and modulator of small G-protein activity, which primarily acts on members of the Rap GTPase subfamily. Via promotion of the active GTP bound conformation of target GTPases, C3G has been implicated in the regulation of multiple cellular and developmental events including proliferation, differentiation and apoptosis. The Drosophila C3G orthologue exhibits a domain organization similar to that of vertebrate C3G. Through deletion of the C3G locus, we have observed that loss of C3G causes semi-lethality, and that escaping adult flies are characterized by a reduction in lifespan and general fitness. In situ hybridization reveals C3G expression in the developing embryonic somatic and visceral muscles, and indeed analysis of C3G mutants suggests essential functions of C3G for normal body wall muscle development during larval stages. C3G mutants display abnormal muscle morphology and attachment, as well as failure to properly localize βPS integrins to muscle attachment sites. Moreover, we show that C3G stimulates guanine nucleotide exchange on Drosophila Rap GTPases in vitro. Taken together, we conclude that Drosophila C3G is a Rap1-specific GEF with important functions in maintaining muscle integrity during larval stages.
Highlights
The ability of a cell to accurately respond to external signals in different developmental contexts relies on the integration of multiple sets of signaling pathways, which in many cases are highly conserved through evolution
To further confirm the specificity of the mutant we investigated the integrity of the neighboring gene on the 39 side by performing RTPCR on mRNA extracted from DC3GMS flies
In this paper we report that loss of the guanine nucleotide exchange factor C3G in Drosophila causes semi-lethality, and that C3G null mutants (DC3GMS) display defects in larval muscle architecture and decreased survival during both larval and adult phases
Summary
The ability of a cell to accurately respond to external signals in different developmental contexts relies on the integration of multiple sets of signaling pathways, which in many cases are highly conserved through evolution. A key event of such cellular signaling is the ligand-mediated activation of receptor tyrosine kinase (RTK) family proteins, leading to the recruitment of a multitude of proteins that function to transmit signals to the proper downstream targets. Essential players in this process include protein and lipid kinases, adaptor and scaffolding molecules, as well as members of the small GTPase superfamily. Small GTPases are monomeric GTP-binding proteins of 20–25kDa, which act as molecular switches during diverse cellular and developmental events, including proliferation, differentiation, apoptosis and control of the cytoskeleton [1].
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