GPCR-Kir channel signaling complexes: defining rules of engagement.
Ion channels and G protein-coupled receptors (GPCRs) are integral transmembrane proteins vital to a multitude of cell signaling and physiological functions. Members of these large protein families are known to interact directly with various intracellular protein partners in a dynamic and isoform-dependent manner, ultimately shaping their life cycle and signal output. The family of G protein-gated inwardly rectifying potassium channels (Kir3 or GIRK) expressed in brain, heart, and endocrine tissues were recently shown to stably associate with several different GPCRs, forming the basis of a macromolecular ion channel-GPCR signaling complex. The molecular determinants that mediate and maintain GPCR-Kir3 channel complexes are currently not well understood. Recent findings and emerging hypotheses on the assembly and stability of multiprotein GPCR-Kir channel signaling complexes are discussed, highlighting distinct mechanisms used by different Kir channel families. These protein-protein interaction processes are crucial in determining both the synaptic response times and the extent of GPCR "cross-talk" in Kir3-mediated inhibitory synaptic transmission.
Doupnik
Craig A
CA
Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida 33612, USA. cdoupnik@health.usf.edu
D000818:Animals; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D020239:Receptor Cross-Talk; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D046912:Multiprotein Complexes; D024661:Potassium Channels, Inwardly Rectifying; D043562:Receptors, G-Protein-Coupled