2023
DOI: 10.1101/2023.01.05.522954
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A self-inactivating invertebrate opsin with resistance to retinal depletion optically drives biased signaling toward Gβγ-dependent ion channel modulation

Abstract: Animal opsins, light-sensitive G protein-coupled receptors (GPCRs), have been utilized for optogenetic tools to control G protein-dependent signaling pathways. Upon G protein activation, the Gα and Gβγ subunits drive different intracellular signaling pathways, leading to complex cellular responses. For some purposes, Gα-, Gβγ- dependent signaling needs to be separately modulated, but these responses are simultaneously evoked due to the 1:1 stoichiometry of Gα and Gβγ. Nevertheless, we show temporal activation … Show more

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Cited by 2 publications
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“…However, potential modulation of cAMP by PdCO activation should not be completely excluded as a variety of ACs have been reported to be affected by different Gα and Gβγ subunits including Gα o 55 . It has also been shown that PdCO can transiently recruit Gα i under long-lasting continuous and/or high-intensity illumination 55,56 , potentially by depleting available Gα o over time and, therefore, generating a signaling bias toward Gα i .…”
Section: Discussionmentioning
confidence: 99%
“…However, potential modulation of cAMP by PdCO activation should not be completely excluded as a variety of ACs have been reported to be affected by different Gα and Gβγ subunits including Gα o 55 . It has also been shown that PdCO can transiently recruit Gα i under long-lasting continuous and/or high-intensity illumination 55,56 , potentially by depleting available Gα o over time and, therefore, generating a signaling bias toward Gα i .…”
Section: Discussionmentioning
confidence: 99%
“…Heterotrimeric G-proteins (G αβγ ) act as signal transducers, enabling the flow of information from the extracellular region to the intracellular downstream effector proteins that control various physiological processes. (1, 2) The process of signal transduction begins upstream, where small molecular agonists, hormones, peptides, light, and other chemical and physical stimuli are received by transmembrane receptor proteins,(3) such as G-protein coupled receptors (GPCRs),(4, 5) ion channels,(6, 7) and enzyme-linked receptors. (8, 9) G-protein-mediated signaling induced by GPCRs is implicated in almost all physiological processes, including vision, gustation, olfaction, immune system regulation, and homeostasis maintenance.…”
Section: Introductionmentioning
confidence: 99%