Prolonged photoresponses and defective adaptation in rods of Gbeta5-/- 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 beta subunit Gbeta5-L. Disruption of the Gbeta5 gene in mice (Gbeta5-/-) abolishes the expression of Gbeta5-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 Gbeta5-/- mice. Responses of Gbeta5-/- rods were indistinguishable in all respects from those of RGS9-/- rods. Loss of Gbeta5-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 Gbeta5-/- 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-Gbeta5-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.
Krispel
Claudia M
CM
Center for Neuroscience, University of California, Davis, Davis, California 95616, USA.
Chen
Ching-Kang
CK
Simon
Melvin I
MI
Burns
Marie E
ME
D000221:Adaptation, Ocular / Q000502:physiology*; D000818:Animals; D003624:Darkness; D044387:GTP-Binding Protein beta Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D066298:In Vitro Techniques; D008027:Light; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D010775:Photic Stimulation; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics; D011930:Reaction Time; D012160:Retina / Q000166:cytology / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D012684:Sensory Thresholds; D015293:Transducin / Q000378:metabolism; D014785:Vision, Ocular / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects
D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D046911:Macromolecular Substances; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin