Competing Activities of Heterotrimeric G Proteins in Drosophila Wing Maturation

Drosophila genome encodes six alpha-subunits of heterotrimeric G proteins. The G alpha s alpha-subunit is involved in the post-eclosion 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 G alpha o can specifically antagonize the G alpha s activities by competing for the G beta 13F/G gamma 1 subunits of the heterotrimeric Gs protein complex. Loss of G beta 13F, G gamma 1, or G alpha s, 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 G alpha s with cholera toxin mimics expression of constitutively activated G alpha s and promotes wing blistering due to precocious cell death. In contrast, co-overexpression of G beta 13F and G gamma 1 does not produce wing blistering, revealing the passive role of the G beta gamma in the G alpha s mediated activation of apoptosis, but hinting at the possible function of G beta gamma 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.