Absence of the RGS9.Gbeta5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse.
Timely termination of the light response in retinal photoreceptors requires rapid inactivation of the G protein transducin. This is achieved through the stimulation of transducin GTPase activity by the complex of the ninth member of the regulator of G protein signaling protein family (RGS9) with type 5 G protein beta subunit (Gbeta5). RGS9.Gbeta5 is anchored to photoreceptor disc membranes by the transmembrane protein, R9AP. In this study, we analyzed visual signaling in the rods of R9AP knockout mice. We found that light responses from R9AP knockout rods were very slow to recover and were indistinguishable from those of RGS9 or Gbeta5 knockout rods. This effect was a consequence of the complete absence of any detectable RGS9 from the retinas of R9AP knockout mice. On the other hand, the level of RGS9 mRNA was not affected by the knockout. These data indicate that in photoreceptors R9AP determines the stability of the RGS9.Gbeta5 complex, and therefore all three proteins, RGS9, Gbeta5 , and R9AP, are obligate members of the regulatory complex that speeds the rate at which transducin hydrolyzes GTP.
Keresztes
Gabor
G
Department of Otolaryngology/Eaton Peabody Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.
Martemyanov
Kirill A
KA
Krispel
Claudia M
CM
Mutai
Hideki
H
Yoo
Peter J
PJ
Maison
Stephane F
SF
Burns
Marie E
ME
Arshavsky
Vadim Y
VY
Heller
Stefan
S
D000818:Animals; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D020710:RGS Proteins / Q000032:analysis / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology
D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D008565:Membrane Proteins; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D020558:GTP Phosphohydrolases