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 (Galphat) is essential for the temporal resolution of rod vision. Regulators of G-protein signalling (RGS) proteins accelerate hydrolysis of GTP by the alpha-subunits of heterotrimeric G proteins in vitro. Several retinal RGS proteins can act in vitro as GTPase accelerating proteins (GAP) for Galphat. Recent reconstitution experiments indicate that one of these, RGS9-1, may account for much of the Galphat GAP activity in rod outer segments (ROS). Here we report that ROS membranes from mice lacking RGS9-1 hydrolyse GTP more slowly than ROS membranes from control mice. The Gbeta5-L protein that forms a complex with RGS9-1 was absent from RGS9-/- retinas, although Gbeta5-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 Gbeta5-L, is essential for acceleration of hydrolysis of GTP by Galphat and for normal recovery of the photoresponse.
Chen
C K
CK
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Burns
M E
ME
He
W
W
Wensel
T G
TG
Baylor
D A
DA
Simon
M I
MI
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism; D015293:Transducin / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*
D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D006160:Guanosine Triphosphate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse; D020558:GTP Phosphohydrolases; D015293:Transducin