Optodynamic simulation of β-adrenergic receptor signalling

Siuda, ER, et al.: 2015 Nature Communications, 6, Art number 9480. DOI: 10.1038/ncomms9480 Read More

Abstract

Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2 AR) is similar in dynamics to endogenous β2 AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2 AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2 ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo. © 2015 Macmillan Publishers Limited. All rights reserved.

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Posted on October 15, 2015
Posted in: Axon Injury & Repair, Neurogenetics, Publications Authors: