title: Nicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel.
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 B3is 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.|Molecular Cellular and Integrative Biosciences Graduate Program, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Awani
authors.initials: A
authors.lastname: Upadhyay
authors.affiliation: Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Pisupati
authors.affiliation: Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Jegla
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Crook
authors.affiliation: Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.|Interdisciplinary Graduate Degree Program in Bioengineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Mickolajczyk
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.|Molecular Cellular and Integrative Biosciences Graduate Program, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Shorey
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Rohan
authors.affiliation: Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Billings
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Rolls
authors.affiliation: Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: William O
authors.initials: WO
authors.lastname: Hancock
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Wendy
authors.identifier: 0000-0002-5566-4758
authors.initials: W
authors.lastname: Hanna-Rose
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism / Q000494:pharmacology*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D012677:Sensation / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C108820:OSM-9 protein, C elegans; D021122:Protein Subunits; D050916:TRPV Cation Channels; D009536:Niacinamide