Abstract
THE photoreceptor G protein, transducin, is one of the class of heterotrimeric G proteins that mediates between membrane receptors and intracellular enzymes or ion channels. Light-activated rhodopsin catalyses the exchange of GDP for GTP on multiple transducin molecules. Activated transducin then stimulates cyclic GMP phosphodiesterase by releasing an inhibitory action of the phosphodiesterase γ-subunits. This leads to a decrease in cGMP levels in the rod, and closure of plasma membrane cationic channels gated by cGMP1–4. In this and other systems, turn-off of the response requires the GTP bound to G protein to be hydrolysed by an intrinsic GTPase activity5–7. Here we report that the interaction of transducin with cGMP phosphodiesterase, specifically with its γ-subunits, accelerates GTPase activity by several fold. Thus the γ-subunits of the phosphodiesterase serve a function analogous to the GTPase-activating proteins that regulate the class of small GTP-binding proteins. The acceleration can be partially suppressed by cGMP, most probably through the non-catalytic cGMP-binding sites of phosphodiesterase α and β-subunits. This cGMP regulation may function in light-adaptation of the photo-response as a negative feedback that decreases the lifetime of activated cGMP phosphodiesterase as light causes decreases in cytoplasmic cGMP.
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Arshavsky, V., Bownds, M. Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP. Nature 357, 416–417 (1992). https://doi.org/10.1038/357416a0
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DOI: https://doi.org/10.1038/357416a0
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