Competing activities of heterotrimeric G proteins in drosophila wing maturation

Abstract

Drosophila genome encodes six alpha-subunits of heterotrimeric G proteins. The Gas alpha-subunit is involved in the posteclosion wing maturation, which consists of the epithelial-mesenchymal transition and cell death, accompanied by unfolding of the pupal wing into the firm adult flight organ. Here we show that another alpha-subunit Gao can specifically antagonize the Gas activities by competing for the Gb13F/Gc1 subunits of the heterotrimeric Gs protein complex. Loss of Gb13F, Gc1, or Gas, but not any other G protein subunit, results in prevention of post-eclosion cell death and failure of the wing expansion. However, cell death prevention alone is not sufficient to induce the expansion defect, suggesting that the failure of epithelial-mesenchymal transition is key to the folded wing phenotypes. Overactivation of Gas with cholera toxin mimics expression of constitutively activated Gas and promotes wing blistering due to precocious cell death. In contrast, cooverexpression of Gb13F and Gc1 does not produce wing blistering, revealing the passive role of the Gbc in the Gasmediated activation of apoptosis, but hinting at the possible function of Gbc in the epithelial-mesenchymal transition. Our results provide a comprehensive functional analysis of the heterotrimeric G protein proteome in the late stages of Drosophila wing development.