RGS7 and RGS8 differentially accelerate G protein-mediated modulation of K+ currents.
The recently discovered family of RGS (regulators of G protein signaling) proteins acts as GTPase activating proteins which bind to alpha subunits of heterotrimeric G proteins. We previously showed that a brain-specific RGS, RGS8 speeds up the activation and deactivation kinetics of the G protein-coupled inward rectifier K+ channel (GIRK) upon receptor stimulation (Saitoh, O., Kubo, Y., Miyatani, Y., Asano, T., and Nakata, H. (1997) Nature 390, 525-529). Here we report the isolation of a full-length rat cDNA of another brain-specific RGS, RGS7. In situ hybridization study revealed that RGS7 mRNA is predominantly expressed in Golgi cells within granule cell layer of cerebellar cortex. We observed that RGS7 recombinant protein binds preferentially to Galphao, Galphai3, and Galphaz. When co-expressed with GIRK1/2 in Xenopus oocytes, RGS7 and RGS8 differentially accelerate G protein-mediated modulation of GIRK. RGS7 clearly accelerated activation of GIRK current similarly with RGS8 but the acceleration effect of deactivation was significantly weaker than that of RGS8. These acceleration properties of RGS proteins may play important roles in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations.
Saitoh
O
O
Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, Tokyo 183-8526, Japan. osaito@tmin.ac.jp
Kubo
Y
Y
Odagiri
M
M
Ichikawa
M
M
Yamagata
K
K
Sekine
T
T
D000595:Amino Acid Sequence; D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D051379:Mice; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D020710:RGS Proteins; D051381:Rats; D016415:Sequence Alignment; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D015221:Potassium Channels; D011506:Proteins; D020710:RGS Proteins; C492038:Rgs7 protein, mouse; C115771:Rgs7 protein, rat; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins