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Nicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel

Author

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  • Awani Upadhyay

    (The Pennsylvania State University
    Molecular Cellular and Integrative Biosciences Graduate Program, The Pennsylvania State University)

  • Aditya Pisupati

    (The Pennsylvania State University)

  • Timothy Jegla

    (The Pennsylvania State University)

  • Matt Crook

    (The Pennsylvania State University
    Present address: Department of Biology, Whitman College, Walla Walla, Washington 99362, USA)

  • Keith J. Mickolajczyk

    (The Pennsylvania State University
    Interdisciplinary Graduate Degree Program in Bioengineering, The Pennsylvania State University)

  • Matthew Shorey

    (The Pennsylvania State University
    Molecular Cellular and Integrative Biosciences Graduate Program, The Pennsylvania State University)

  • Laura E. Rohan

    (The Pennsylvania State University)

  • Katherine A. Billings

    (The Pennsylvania State University)

  • Melissa M. Rolls

    (The Pennsylvania State University)

  • William O. Hancock

    (The Pennsylvania State University)

  • Wendy Hanna-Rose

    (The Pennsylvania State University)

Abstract

TRPV ion channels are directly activated by sensory stimuli and participate in thermo-, mechano- and chemo-sensation. They are also hypothesized to respond to endogenous agonists that would modulate sensory responses. Here, we show that the nicotinamide (NAM) form of vitamin B3 is an agonist of a Caenorhabditis elegans TRPV channel. Using heterologous expression in Xenopus oocytes, we demonstrate that NAM is a soluble agonist for a channel consisting of the well-studied OSM-9 TRPV subunit and relatively uncharacterized OCR-4 TRPV subunit as well as the orthologous Drosophila Nan-Iav TRPV channel, and we examine stoichiometry of subunit assembly. Finally, we show that behaviours mediated by these C. elegans and Drosophila channels are responsive to NAM, suggesting conservation of activity of this soluble endogenous metabolite on TRPV activity. Our results in combination with the role of NAM in NAD+ metabolism suggest an intriguing link between metabolic regulation and TRPV channel activity.

Suggested Citation

  • Awani Upadhyay & Aditya Pisupati & Timothy Jegla & Matt Crook & Keith J. Mickolajczyk & Matthew Shorey & Laura E. Rohan & Katherine A. Billings & Melissa M. Rolls & William O. Hancock & Wendy Hanna-Ro, 2016. "Nicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel," Nature Communications, Nature, vol. 7(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13135
    DOI: 10.1038/ncomms13135
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    Cited by:

    1. Martina Nicoletti & Letizia Chiodo & Alessandro Loppini, 2021. "Biophysics and Modeling of Mechanotransduction in Neurons: A Review," Mathematics, MDPI, vol. 9(4), pages 1-32, February.

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