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Optogenetic Inhibition of G?q Protein Signaling Reduces Calcium Oscillation Stochasticity.


ABSTRACT: As fast terminators of G-protein coupled receptor (GPCR) signaling, regulators of G-protein signaling (RGS) serve critical roles in fine-tuning second messenger levels and, consequently, cellular responses to external stimuli. Here, we report the creation of an optogenetic RGS2 (opto-RGS2) that suppresses agonist-evoked calcium oscillations by the inactivation of G?q protein. In this system, cryptochrome-mediated heterodimerization of the catalytic RGS2-box with its N-terminal amphipathic helix reconstitutes a functional membrane-localized complex that can dynamically suppress store-operated release of calcium. Engineered opto-RGS2 cell lines were used to establish the role of RGS2 as a key inhibitory feedback regulator of the stochasticity of the G?q-mediated calcium spike timing. RGS2 reduced the stochasticity of carbachol-stimulated calcium oscillations, and the feedback inhibition was coupled to the global calcium elevation by calmodulin/RGS2 interactions. The identification of a critical negative feedback circuit exemplifies the utility of optogenetic approaches for interrogating RGS/GPCR biology and calcium encoding principles through temporally precise molecular gain-of-function.

SUBMITTER: Hannanta-Anan P 

PROVIDER: S-EPMC6311707 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Optogenetic Inhibition of Gα<sub>q</sub> Protein Signaling Reduces Calcium Oscillation Stochasticity.

Hannanta-Anan Pimkhuan P   Chow Brian Y BY  

ACS synthetic biology 20180604 6


As fast terminators of G-protein coupled receptor (GPCR) signaling, regulators of G-protein signaling (RGS) serve critical roles in fine-tuning second messenger levels and, consequently, cellular responses to external stimuli. Here, we report the creation of an optogenetic RGS2 (opto-RGS2) that suppresses agonist-evoked calcium oscillations by the inactivation of Gα<sub>q</sub> protein. In this system, cryptochrome-mediated heterodimerization of the catalytic RGS2-box with its N-terminal amphipa  ...[more]

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