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Interaction between the RGS domain of RGS4 with G protein alpha subunits mediates the voltage-dependent relaxation of the G protein-gated potassium channel.
Inanobe A
,
Fujita S
,
Makino Y
,
Matsushita K
,
Ishii M
,
Chachin M
,
Kurachi Y
.
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1. In native cardiac myocytes, there is a time dependence to the G protein-gated inwardly rectifying K(+) (K(G)) channel current during voltage steps that accelerates as the concentration of acetylcholine is increased. This phenomenon has been called 'relaxation' and is not reproduced in the reconstituted Kir3.1/Kir3.4 channel in Xenopus oocytes. We have shown that RGS4, a regulator of G protein signalling, restores relaxation to the reconstituted Kir3.1/Kir3.4 channel. In this study, we examined the mechanism of this phenomenon by expressing various combinations of membrane receptors, G proteins, Kir3.0 subunits and mutants of RGS4 in Xenopus oocytes. 2. RGS4 restored relaxation to K(G) channels activated by the pertussis toxin (PTX)-sensitive G protein-coupled m(2)-muscarinic receptor but not to those activated by the G(s) protein-coupled beta(2)-adrenergic receptor. 3. RGS4 induced relaxation not only in heteromeric K(G) channels composed of Kir3.1 and Kir3.4 but also in homomeric assemblies of either an active mutant of Kir3.1 (Kir3.1/F137S) or an isoform of Kir3.2 (Kir3.2d). 4. Truncation mutants of RGS4 showed that the RGS domain itself was essential to reproduce the effect of wild-type RGS4 on the K(G) channel. 5. The mutation of residues in the RGS domain which interact with the alpha subunit of the G protein (G(alpha)) impaired the effect of RGS4. 6. This study therefore shows that interaction between the RGS domain and PTX-sensitive G(alpha) subunits mediates the effect of RGS4 on the agonist concentration-dependent relaxation of K(G) channels.
Bernstein,
RGS4 binds to membranes through an amphipathic alpha -helix.
2000, Pubmed
Bernstein,
RGS4 binds to membranes through an amphipathic alpha -helix.
2000,
Pubmed
Bünemann,
Regulators of G protein signaling (RGS) proteins constitutively activate Gbeta gamma-gated potassium channels.
1998,
Pubmed
Chan,
Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K+ channel subunit.
1996,
Pubmed
,
Xenbase
Chuang,
Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels.
1998,
Pubmed
Doupnik,
RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels.
1997,
Pubmed
,
Xenbase
Fujita,
A regulator of G protein signalling (RGS) protein confers agonist-dependent relaxation gating to a G protein-gated K+ channel.
2000,
Pubmed
,
Xenbase
Hedin,
Cloning of a Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes.
1996,
Pubmed
,
Xenbase
Hepler,
Emerging roles for RGS proteins in cell signalling.
1999,
Pubmed
Herlitze,
New roles for RGS2, 5 and 8 on the ratio-dependent modulation of recombinant GIRK channels expressed in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Inanobe,
Molecular cloning and characterization of a novel splicing variant of the Kir3.2 subunit predominantly expressed in mouse testis.
1999,
Pubmed
,
Xenbase
Krapivinsky,
The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.
1995,
Pubmed
,
Xenbase
Kubo,
Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel.
1993,
Pubmed
,
Xenbase
Lancaster,
Residues and mechanisms for slow activation and Ba2+ block of the cardiac muscarinic K+ channel, Kir3.1/Kir3.4.
2000,
Pubmed
,
Xenbase
Lesage,
Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain.
1994,
Pubmed
,
Xenbase
Lesage,
Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels.
1995,
Pubmed
,
Xenbase
Müllner,
Heterologous facilitation of G protein-activated K(+) channels by beta-adrenergic stimulation via cAMP-dependent protein kinase.
2000,
Pubmed
,
Xenbase
Natochin,
Mutational analysis of the Asn residue essential for RGS protein binding to G-proteins.
1998,
Pubmed
Noma,
Relaxation of the ACh-induced potassium current in the rabbit sinoatrial node cell.
1978,
Pubmed
Popov,
Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity.
2000,
Pubmed
Popov,
The regulators of G protein signaling (RGS) domains of RGS4, RGS10, and GAIP retain GTPase activating protein activity in vitro.
1997,
Pubmed
Saitoh,
RGS8 accelerates G-protein-mediated modulation of K+ currents.
1997,
Pubmed
,
Xenbase
Saitoh,
RGS7 and RGS8 differentially accelerate G protein-mediated modulation of K+ currents.
1999,
Pubmed
,
Xenbase
Spink,
Structural basis of the Axin-adenomatous polyposis coli interaction.
2000,
Pubmed
,
Xenbase
Srinivasa,
Mechanism of RGS4, a GTPase-activating protein for G protein alpha subunits.
1998,
Pubmed
Tesmer,
Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis.
1997,
Pubmed
Tu,
Palmitoylation of a conserved cysteine in the regulator of G protein signaling (RGS) domain modulates the GTPase-activating activity of RGS4 and RGS10.
1999,
Pubmed
Yamada,
G protein regulation of potassium ion channels.
1998,
Pubmed
Zeng,
The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling.
1998,
Pubmed
Zheng,
Divergence of RGS proteins: evidence for the existence of six mammalian RGS subfamilies.
1999,
Pubmed
de Alba,
Solution structure of human GAIP (Galpha interacting protein): a regulator of G protein signaling.
1999,
Pubmed
