Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1

Timely deactivation of the alpha-subunit of the rod G-protein transducin (G alpha t) is essential for the temporal resolution of rod vision(1). Regulators of G-protein signalling (RGS) proteins accelerate hydrolysis of GTP by the alpha-subunits of heterotrimeric G proteins(2-4) in vitro. Several retinal RGS proteins can act in vitro as GTPase accelerating proteins (GAP) for G alpha t(5-8). Recent reconstitution experiments indicate that one of these, RGS9-1, may account for much of the G alpha t GAP activity in rod outer segments (ROS)(8,9). Here we report that ROS membranes from mice lacking RGS9-1 hydrolyse GTP more slowly than ROS membranes from control mice. The G beta 5-L protein that forms a complex with RGS9-1 (ref. 10) was absent from RGS9(-/-) retinas, although G beta 5-L messenger RNA was still present. The flash responses of RGS9(-/-) rods rose normally, but recovered much more slowly than normal. We conclude that RGS9-1, probably in a complex with G beta 5-L, is essential for acceleration of hydrolysis of GTP by G alpha t and for normal recovery of the photoresponse.