G?q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila

Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein?coupled receptors to intracellular effector molecules. In Drosophila, the G?q gene encodes several G?q splice variants, with the G?q1 isoform protein playing a major role in fly phototransduction. However, G?q1 null mutant flies still exhibit a residual light response, indicating that other G?q splice variants or additional Gq ? subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the G?q gene disrupt light responses and demonstrate that the G?q3 isoform protein is responsible for the residual light response in G?q1 null mutants. Moreover, we report that G?q3 mediates rhodopsin synthesis. Depletion of all G?q splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different G?q splice variants in phototransduction and retinal integrity in Drosophila and reveal that G?q3 functions in rhodopsin synthesis.