ARRESTIN FUNCTION IN INACTIVATION OF G-PROTEIN COUPLED RECEPTOR RHODOPSIN INVIVO

Arrestins have been implicated in the regulation of many G protein-cou pled receptor signaling cascades. Mutations in two Drosophila photorec eptor-specific arrestin genes, arrestin 1 and arrestin 2, were generat ed. Analysis of the light response in these mutants shows that the Arr 1 and Arr2 proteins are mediators of rhodopsin inactivation and are es sential for the termination of the phototransduction cascade in vivo. The saturation of arrestin function by an excess of activated rhodopsi n is responsible for a continuously activated state of the photorecept ors known as the prolonged depolarized afterpotential. In the absence of arrestins, photoreceptors undergo light-dependent retinal degenerat ion as a result of the continued activity of the phototransduction cas cade. These results demonstrate the fundamental requirement for member s of the arrestin protein family in the regulation of G protein-couple d receptors and signaling cascades in vivo.