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- Title
Selective optogenetic control of G<sub>q</sub> signaling using human Neuropsin.
- 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
- 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. Gq proteins are one of four major classes of G proteins; optogenetic receptors for selective and repetitive activation of Gq proteins with fast kinetics are lacking. Here the authors report UV light-dependent Gq signalling using human Neuropsin (hOPN5) and demonstrate its potential as an optogenetic tool.
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Academic Journal
- DOI
10.1038/s41467-022-29265-w