| http://purl.uniprot.org/citations/23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23169654 | http://www.w3.org/2000/01/rdf-schema#comment | "G-protein-activated inward-rectifying K(+) (GIRK) channels hyperpolarize neurons to inhibit synaptic transmission throughout the nervous system. By accelerating G-protein deactivation kinetics, the regulator of G-protein signaling (RGS) protein family modulates the timing of GIRK activity. Despite many investigations, whether RGS proteins modulate GIRK activity in neurons by mechanisms involving kinetic coupling, collision coupling, or macromolecular complex formation has remained unknown. Here we show that GIRK modulation occurs by channel assembly with R7-RGS/Gβ5 complexes under allosteric control of R7 RGS-binding protein (R7BP). Elimination of R7BP occludes the Gβ5 subunit that interacts with GIRK channels. R7BP-bound R7-RGS/Gβ5 complexes and Gβγ dimers interact noncompetitively with the intracellular domain of GIRK channels to facilitate rapid activation and deactivation of GIRK currents. By disrupting this allosterically regulated assembly mechanism, R7BP ablation augments GIRK activity. This enhanced GIRK activity increases the drug effects of agonists acting at G-protein-coupled receptors that signal via GIRK channels, as indicated by greater antinociceptive effects of GABA(B) or μ-opioid receptor agonists. These findings show that GIRK current modulation in vivo requires channel assembly with allosterically regulated RGS protein complexes, which provide a target for modulating GIRK activity in neurological disorders in which these channels have crucial roles, including pain, epilepsy, Parkinson's disease and Down syndrome."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1214337109"xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/author | "Zhou H."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/author | "Blumer K.J."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/author | "Bohn L.M."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/author | "Kaltenbronn K.M."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/author | "Raehal K.M."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/author | "Chisari M."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/author | "Mennerick S.J."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/pages | "19977-19982"xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/title | "GIRK channel modulation by assembly with allosterically regulated RGS proteins."xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://purl.uniprot.org/core/volume | "109"xsd:string |
| http://purl.uniprot.org/citations/23169654 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23169654 |
| http://purl.uniprot.org/citations/23169654 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23169654 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J239-mappedCitation-23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23169654 |
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| http://purl.uniprot.org/uniprot/#_Q0VB45-mappedCitation-23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23169654 |
| http://purl.uniprot.org/uniprot/#_A0A338P6L0-mappedCitation-23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23169654 |
| http://purl.uniprot.org/uniprot/#_Q3UG14-mappedCitation-23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23169654 |
| http://purl.uniprot.org/uniprot/#_Q8BQP9-mappedCitation-23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23169654 |
| http://purl.uniprot.org/uniprot/#_P48542-mappedCitation-23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23169654 |
| http://purl.uniprot.org/uniprot/#_P62881-mappedCitation-23169654 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23169654 |