Optodynamic simulation of β-adrenergic receptor signalling

Edward R. Siuda, Jordan G. McCall, Ream Al-Hasani, Gunchul Shin, Sung Il Park, Martin J. Schmidt, Sonya L. Anderson, William J. Planer, John A. Rogers and Michael R. Bruchas ()
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Edward R. Siuda: Washington University School of Medicine
Jordan G. McCall: Washington University School of Medicine
Ream Al-Hasani: Washington University School of Medicine
Gunchul Shin: Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign
Sung Il Park: Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign
Martin J. Schmidt: Washington University School of Medicine
Sonya L. Anderson: Washington University School of Medicine
William J. Planer: Washington University School of Medicine
John A. Rogers: Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign
Michael R. Bruchas: Washington University School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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-β2AR) is similar in dynamics to endogenous β2AR 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-β2AR 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 β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo.

Date: 2015
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DOI: 10.1038/ncomms9480

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