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Selective optogenetic control of Gq signaling using human Neuropsin

Author

Listed:
  • Ahmed Wagdi

    (University Medical Center Göttingen
    German Center for Cardiovascular Research (DZHK), Partner site Göttingen
    University Medical Center Göttingen, Georg August University of Göttingen)

  • Daniela Malan

    (University of Bonn)

  • Udhayabhaskar Sathyanarayanan

    (University Medical Center Göttingen)

  • Janosch S. Beauchamp

    (University Medical Center Göttingen)

  • Markus Vogt

    (University Medical Center Göttingen)

  • David Zipf

    (University Medical Center Göttingen)

  • Thomas Beiert

    (University Hospital Bonn, University of Bonn)

  • Berivan Mansuroglu

    (University of Bonn
    University of Bonn)

  • Vanessa Dusend

    (University of Bonn
    University of Bonn)

  • Mark Meininghaus

    (Bayer AG, Research & Development, Pharmaceuticals)

  • Linn Schneider

    (Bayer AG, Research & Development, Pharmaceuticals)

  • Bernd Kalthof

    (Bayer AG, Research & Development, Pharmaceuticals)

  • J. Simon Wiegert

    (University Medical Center Hamburg-Eppendorf)

  • Gabriele M. König

    (University of Bonn)

  • Evi Kostenis

    (University of Bonn)

  • Robert Patejdl

    (Rostock University Medical Center)

  • Philipp Sasse

    (University of Bonn)

  • Tobias Bruegmann

    (University Medical Center Göttingen
    German Center for Cardiovascular Research (DZHK), Partner site Göttingen
    University of Bonn
    University of Bonn)

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.

Suggested Citation

  • Ahmed Wagdi & Daniela Malan & Udhayabhaskar Sathyanarayanan & Janosch S. Beauchamp & Markus Vogt & David Zipf & Thomas Beiert & Berivan Mansuroglu & Vanessa Dusend & Mark Meininghaus & Linn Schneider , 2022. "Selective optogenetic control of Gq signaling using human Neuropsin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29265-w
    DOI: 10.1038/s41467-022-29265-w
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    References listed on IDEAS

    as
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