Key result
Recent findings and emerging hypotheses highlight distinct mechanisms used by different Kir channel families in the assembly and stability of multiprotein GPCR-Kir channel signaling complexes.
Provides a conceptual overview of the molecular determinants that mediate and maintain GPCR-Kir3 channel complexes, which are crucial for cell signaling in cardiac and neural tissues.
May guide selective GPCR-Kir modulators in cardiac disease; leaves open in vivo validation.
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.
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Craig A. Doupnik (2008) reported a review. Recent findings and emerging hypotheses highlight distinct mechanisms used by different Kir channel families in the assembly and stability of multiprotein GPCR-Kir channel signaling complexes.
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