Competing Activities of Heterotrimeric G Proteins in Drosophila Wing Maturation

Abstract

Drosophila genome encodes six alpha-subunits of heterotrimeric G proteins. The Gαs 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 Gαo can specifically antagonize the Gαs activities by competing for the Gβ13F/Gγ1 subunits of the heterotrimeric Gs protein complex. Loss of Gβ13F, Gγ1, or Gαs, 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 Gαs with cholera toxin mimics expression of constitutively activated Gαs and promotes wing blistering due to precocious cell death. In contrast, co-overexpression of Gβ13F and Gγ1 does not produce wing blistering, revealing the passive role of the Gβγ in the Gαs-mediated activation of apoptosis, but hinting at the possible function of Gβγ 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.

Outside-in signaling – a brief review of GPCR signaling with a focus on the Drosophila GPCR family

“…Not surprisingly, modulators of GPCR signaling, such as GRKs, GDIs, GPCR kinases and arrestins, are also encoded in the Drosophila genome. One aspect of Drosophila GPCR signaling that makes it particularly appealing for study is the reduced number of G-proteins -nine genes encode predicted Gα proteins (six have been characterized and three are known only by their CG numbers), three genes encode Gβ proteins and two genes encode Gγ proteins (Table 1) (Katanayeva et al, 2010;Anantharaman et al, 2011). Of the three Gα subunits with only CG designations, one appears to be a pseudogene (CG40005) and the other two are not expressed in embryos (CG30054 and CG17760).…”

The Expanding Roles of GβγSubunits in G Protein–Coupled Receptor Signaling and Drug Action

“…As in C. elegans, Gbg dimers are involved in the control of asymmetric cell division in neuroblasts and sensory organs, gastrulation, heart function (Schaefer et al, 2001;Izumi et al, 2004;Yi et al, 2006Yi et al, , 2008, and the visual system (Dolph et al, 1994;Schulz et al, 1999). One study suggested that free Gbg subunits are involved in wing expansion accompanied by epithelial-mesenchymal transition (Katanayeva et al, 2010). Beyond this role in early development, Gbg subunits also serve other canonical roles in GPCR signaling in the adult fly, as in C. elegans.…”

Yellow submarine of the Wnt/Frizzled signaling: Submerging from the G protein harbor to the targets

“…Indeed, in the brain Gbg released from the Go complex is able to regulate voltage-dependent Ca 2+ channels, as well as inward-rectifier K + channels [132]. However, through several broad screening approaches we have identified a massive network of Gao-centered protein-protein interactions ( [121,133] and unpublished data). Two novel Gao target proteins will be reviewed below: Rab5 and Axin.…”