Selective optogenetic control of Gq signaling using human Neuropsin

• Published in: Nature communications Vol. 13; no. 1; p. 1765
• Main Authors: Wagdi, Ahmed, Malan, Daniela, Sathyanarayanan, Udhayabhaskar, Beauchamp, Janosch S., Vogt, Markus, Zipf, David, Beiert, Thomas, Mansuroglu, Berivan, Dusend, Vanessa, Meininghaus, Mark, Schneider, Linn, Kalthof, Bernd, Wiegert, J. Simon, König, Gabriele M., Kostenis, Evi, Patejdl, Robert, Sasse, Philipp, Bruegmann, Tobias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.04.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animal models; Calcium ions; Channel gating; Genetic transformation; High-throughput screening; Intestine; Intracellular signalling; Kinetics; Mammalian cells; Pharmacology; Potassium channels (inwardly-rectifying); Proteins; Screening; Signal transduction; Signaling; Small intestine; Temporal resolution; Transgenic animals; Ultraviolet radiation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29265-w

Abstract G q proteins are universally important for signal transduction in mammalian cells. The underlying kinetics and transformation from extracellular stimuli into intracellular signaling, however could not be investigated in detail so far. Here we present the human Neuropsin (hOPN5) for specific and repetitive manipulation of G q signaling in vitro and in vivo with high spatio-temporal resolution. Properties and G protein specificity of hOPN5 are characterized by UV light induced IP 3 generation, Ca 2+ transients and inhibition of G IRK channel activity in HEK cells. In adult hearts from a transgenic animal model, light increases the spontaneous beating rate. In addition, we demonstrate light induced contractions in the small intestine, which are not detectable after pharmacological G q protein block. All-optical high-throughput screening for TRPC6 inhibitors is more specific and sensitive than conventional pharmacological screening. Thus, we demonstrate specific G q signaling of hOPN5 and unveil its potential for optogenetic applications.