Optogenetic interrogation reveals separable G-protein-dependent and -independent signalling linking G-protein-coupled receptors to the circadian oscillator
Posted on 2017-05-15 - 05:00
Abstract Background Endogenous circadian oscillators distributed across the mammalian body are synchronised among themselves and with external time via a variety of signalling molecules, some of which interact with G-protein-coupled receptors (GPCRs). GPCRs can regulate cell physiology via pathways originating with heterotrimeric G-proteins or β-arrestins. We applied an optogenetic approach to determine the contribution of these two signalling modes on circadian phase. Results We employed a photopigment (JellyOp) that activates Gαs signalling with better selectivity and higher sensitivity than available alternatives, and a point mutant of this pigment (F112A) biased towards β-arrestin signalling. When expressed in fibroblasts, both native JellyOp and the F112A arrestin-biased mutant drove light-dependent phase resetting in the circadian clock. Shifts induced by the two opsins differed in their circadian phase dependence and the degree to which they were associated with clock gene induction. Conclusions Our data imply separable G-protein and arrestin inputs to the mammalian circadian clock and establish a pair of optogenetic tools suitable for manipulating Gαs- and β-arrestin-biased signalling in live cells.
CITE THIS COLLECTION
3D Printing in Medicine
3D-Printed Materials and Systems
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Bailes, Helena; Milosavljevic, Nina; Zhuang, Ling-Yu; Gerrard, Elliot; Nishiguchi, Tomoki; Ozawa, Takeaki; et al. (2017). Optogenetic interrogation reveals separable G-protein-dependent and -independent signalling linking G-protein-coupled receptors to the circadian oscillator. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.3780035.v1
Select your citation style and then place your mouse over the citation text to select it.