Molecular basis of signaling specificity between GIRK channels and GPCRs.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30526853.
- Also identified by DOI 10.7554/eLife.42908 and PMC identifier 6335053.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Stimulated muscarinic acetylcholine receptors (M2Rs) release Gβγ subunits, which slow heart rate by activating a G protein-gated K<sup>+</sup> channel (GIRK). Stimulated β2 adrenergic receptors (β2ARs) also release Gβγ subunits, but GIRK is not activated. This study addresses the mechanism underlying this specificity of GIRK activation by M2Rs. K<sup>+</sup> currents and bioluminescence resonance energy transfer between labelled G proteins and GIRK show that M2Rs catalyze Gβγ subunit release at higher rates than β2ARs, generating higher Gβγ concentrations that activate GIRK and regulate other targets of Gβγ. The higher rate of Gβγ release is attributable to a faster G protein coupled receptor - G protein trimer association rate in M2R compared to β2AR. Thus, a rate difference in a single kinetic step accounts for specificity.
Medical subject headings
- G Protein-Coupled Inwardly-Rectifying Potassium Channels
- Receptors, G-Protein-Coupled
- Signal Transduction