Why the study?
Mechanisms promoting the compartmentalization of G-protein signaling were poorly understood in native cells.
RGS6 shapes GIRK-dependent signaling dynamics in the mouse heart through GPCR-G protein signaling and RGS-G protein substrate biases.
Significance Mechanisms promoting the compartmentalization of G-protein signaling are poorly understood in native cells. This study examined muscarinic (M 2 R) and adenosine (A 1 R) receptor signaling to a common effector—the G protein-gated inwardly rectifying K + (GIRK) channel—in mouse sino-atrial nodal (SAN) cells. Regulator of G protein Signaling 6 (RGS6) exerts a GPCR-dependent influence on the efficacy, kinetics, and sensitivity of GIRK-dependent signaling in SAN cells, suppressing M 2 R-GIRK signaling kinetics and sensitivity and A 1 R-GIRK signaling amplitude. The distinctions can be explained by the differential utilization of G protein isoforms by M 2 R and A 1 R and a Gα o substrate preference of RGS6. Thus, GPCR-G protein signaling and RGS-G protein substrate biases shape GIRK-dependent signaling dynamics in the mouse heart.
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Anderson et al. (2020) studied this question.
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