Selective optogenetic control of Gq signaling using human Neuropsin

Authors

Wagdi A, Malan D, Sathyanarayanan U, Beauchamp JS, Vogt M, Zipf D, Beiert T, Mansuroglu B, Dusend V, Meininghaus M, Schneider L, Kalthof B, Wiegert JS, König GM, Kostenis E, Patejdl R, Sasse P, Bruegmann T

Journal

Nature Communications

Citation

Nat Commun. 2022 Apr 1;13(1):1765.
Author Correction: Nat Commun. 2023 Jan 4;14(1):58.

Abstract

Gq 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 Gq signaling in vitro and in vivo with high spatio-temporal resolution. Properties and G protein specificity of hOPN5 are characterized by UV light induced IP3 generation, Ca2+ transients and inhibition of GIRK 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 Gq protein block. All-optical high-throughput screening for TRPC6 inhibitors is more specific and sensitive than conventional pharmacological screening. Thus, we demonstrate specific Gq signaling of hOPN5 and unveil its potential for optogenetic applications.