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Curr Pharm Biotechnol
2014 Jan 01;1510:987-95. doi: 10.2174/1389201015666141031111916.
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G protein-coupled receptor signaling to Kir channels in Xenopus oocytes.
Hatcher-Solis C, Fribourg M, Spyridaki K, Younkin J, Ellaithy A, Xiang G, Liapakis G, Gonzalez-Maeso J, Zhang H, Cui M, Logothetis DE.
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Kir3 (or GIRK) channels have been known for nearly three decades to be activated by direct interactions with the βγ subunits of heterotrimeric G (Gαβγ) proteins in a membrane-delimited manner. Gα also interacts with GIRK channels and since PTX-sensitive Gα subunits show higher affinity of interaction they confer signaling specificity to G Protein- Coupled Receptors (GPCRs) that normally couple to these G protein subunits. In heterologous systems, overexpression of non PTX-sensitive Gα subunits scavenges the available Gβγ and biases GIRK activation through GPCRs that couple to these Gα subunits. Moreover, all Kir channels rely on their direct interactions with the phospholipid PIP2 to maintain their activity. Thus, signals that activate phospholipase C (e.g. through Gq signaling) to hydrolyze PIP2 result in inhibition of Kir channel activity. In this review, we illustrate with experiments performed in Xenopus oocytes that Kir channels can be used efficiently as reporters of GPCR function through Gi, Gs or Gq signaling. The membrane-delimited nature of this expression system makes it highly efficient for constructing dose-response curves yielding highly reproducible apparent affinities of different ligands for each GPCR tested.
Barnard,
Translation of exogenous messenger RNA coding for nicotinic acetylcholine receptors produces functional receptors in Xenopus oocytes.
1982, Pubmed,
Xenbase
Barnard,
Translation of exogenous messenger RNA coding for nicotinic acetylcholine receptors produces functional receptors in Xenopus oocytes.
1982,
Pubmed
,
Xenbase Birnbaumer,
Receptor-effector coupling by G proteins.
1990,
Pubmed Breitwieser,
Uncoupling of cardiac muscarinic and beta-adrenergic receptors from ion channels by a guanine nucleotide analogue.
,
Pubmed Chan,
A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins.
1996,
Pubmed
,
Xenbase Daaka,
Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A.
1997,
Pubmed Dascal,
Expression of an atrial G-protein-activated potassium channel in Xenopus oocytes.
1993,
Pubmed
,
Xenbase Du,
Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators.
2004,
Pubmed
,
Xenbase Fribourg,
Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs.
2011,
Pubmed
,
Xenbase Gundersen,
Messenger RNA from human brain induces drug- and voltage-operated channels in Xenopus oocytes.
,
Pubmed
,
Xenbase Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed Hansen,
Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2.
2011,
Pubmed Hedin,
Cloning of a Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes.
1996,
Pubmed
,
Xenbase Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase Kehrl,
RGS2: a multifunctional regulator of G-protein signaling.
2002,
Pubmed Keselman,
Mechanism of PLC-mediated Kir3 current inhibition.
2007,
Pubmed Kobrinsky,
Receptor-mediated hydrolysis of plasma membrane messenger PIP2 leads to K+-current desensitization.
2000,
Pubmed
,
Xenbase Kubo,
Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel.
1993,
Pubmed
,
Xenbase Kurachi,
Acetylcholine activation of K+ channels in cell-free membrane of atrial cells.
1986,
Pubmed Lefkowitz,
Seven transmembrane receptors: something old, something new.
2007,
Pubmed Lim,
A G protein-gated K channel is activated via beta 2-adrenergic receptors and G beta gamma subunits in Xenopus oocytes.
1995,
Pubmed
,
Xenbase Lin,
G-protein-coupled receptors and their (Bio) chemical significance win 2012 Nobel Prize in Chemistry.
2013,
Pubmed Logothetis,
The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart.
,
Pubmed Mahajan,
A computational model predicts that Gβγ acts at a cleft between channel subunits to activate GIRK1 channels.
2013,
Pubmed Meng,
The molecular mechanism by which PIP(2) opens the intracellular G-loop gate of a Kir3.1 channel.
2012,
Pubmed Methfessel,
Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels.
1986,
Pubmed
,
Xenbase Miledi,
Properties of acetylcholine receptors translated by cat muscle mRNA in Xenopus oocytes.
1982,
Pubmed
,
Xenbase Milligan,
Heterotrimeric G-proteins: a short history.
2006,
Pubmed Petit-Jacques,
Synergistic activation of G protein-gated inwardly rectifying potassium channels by the betagamma subunits of G proteins and Na(+) and Mg(2+) ions.
1999,
Pubmed
,
Xenbase Pfaffinger,
GTP-binding proteins couple cardiac muscarinic receptors to a K channel.
,
Pubmed Rohács,
PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain.
2005,
Pubmed Soejima,
Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells.
1984,
Pubmed Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase Vivaudou,
Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants.
1997,
Pubmed
,
Xenbase Whorton,
X-ray structure of the mammalian GIRK2-βγ G-protein complex.
2013,
Pubmed Whorton,
Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.
2011,
Pubmed
,
Xenbase
