Selective optogenetic control of Gq signaling using human Neuropsin
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Selective optogenetic control of Gq signaling using human Neuropsin. / 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.
in: NAT COMMUN, Jahrgang 13, Nr. 1, 1765, 01.04.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Selective optogenetic control of Gq signaling using human Neuropsin
AU - Wagdi, Ahmed
AU - Malan, Daniela
AU - Sathyanarayanan, Udhayabhaskar
AU - Beauchamp, Janosch S
AU - Vogt, Markus
AU - Zipf, David
AU - Beiert, Thomas
AU - Mansuroglu, Berivan
AU - Dusend, Vanessa
AU - Meininghaus, Mark
AU - Schneider, Linn
AU - Kalthof, Bernd
AU - Wiegert, J Simon
AU - König, Gabriele M
AU - Kostenis, Evi
AU - Patejdl, Robert
AU - Sasse, Philipp
AU - Bruegmann, Tobias
N1 - © 2022. The Author(s).
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-29265-w
DO - 10.1038/s41467-022-29265-w
M3 - SCORING: Journal article
C2 - 35365606
VL - 13
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
M1 - 1765
ER -