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, Michael R. Bruchas*

*Corresponding author for this work

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Article number8480
JournalNature communications
Volume6
DOIs
StatePublished - Sep 28 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Siuda, E. R., McCall, J. G., Al-Hasani, R., Shin, G., Park, S. I., Schmidt, M. J., Anderson, S. L., Planer, W. J., Rogers, J. A., & Bruchas, M. R. (2015). Optodynamic simulation of β-adrenergic receptor signalling. Nature communications, 6, [8480]. https://doi.org/10.1038/ncomms9480