Prolonged photoresponses and defective adaptation in rods of Gβ5 ^-/- mice

Timely deactivation of G-protein signaling is essential for the proper function of many cells, particularly neurons. Termination of the light response of retinal rods requires GTP hydrolysis by the G-protein transducin, which is catalyzed by a protein complex that includes regulator of G-protein signaling RGS9-1 and the G-protein β subunit Gβ5-L. Disruption of the Gβ5 gene in mice (Gβ5^-/-) abolishes the expression of Gβ5-L in the retina and also greatly reduces the expression level of RGS9-1. We examined transduction in dark- and light-adapted rods from wild-type and Gβ5 ^-/- mice. Responses of Gβ5^-/- rods were indistinguishable in all respects from those of RGS9^-/- rods. Loss of Gβ5-L (and RGS9-1) had no effect on the activation of the G-protein cascade, but profoundly slowed its deactivation and interfered with the speeding of incremental dim flashes during light adaptation. Both RGS9 ^-/- and Gβ5^-/- responses were consistent with another factor weakly regulating GTP hydrolysis by transducin in a manner proportional to the inward current. Our results indicate that a complex containing RGS9-1-Gβ5-L is essential for normal G-protein deactivation and rod function. In addition, our light adaptation studies support the notion than an additional weak GTPase-accelerating factor in rods is regulated by intracellular calcium and/or cGMP.