title: Polymodal sensory function of the Caenorhabditis elegans OCR-2 channel arises from distinct intrinsic determinants within the protein and is selectively conserved in mammalian TRPV proteins.
abstract: Caenorhabditis elegans OCR-2 (OSM-9 and capsaicin receptor-related) is a TRPV (vanilloid subfamily of transient receptor potential channel) protein that regulates serotonin (5-HT) biosynthesis in chemosensory neurons and also mediates olfactory and osmotic sensation. Here, we identify the molecular basis for the polymodal function of OCR-2 in its native cellular environment. We show that OCR-2 function in 5-HT production and osmotic sensing is governed by its N-terminal region upstream of the ankyrin repeats domain, but the diacetyl sensitivity is mediated by independent mechanisms. The ocr-2(yz5) mutation results in a glycine-to-glutamate substitution (G36E) within the N-terminal region. The G36E substitution causes dramatic downregulation of 5-HT synthesis in the ADF neurons, eliminates osmosensation mediated by the ASH neurons, but does not affect the response to the odorant diacetyl mediated by the AWA neurons. Conversely, wild-type sequence of the N-terminal segment confers osmotic sensitivity and upregulation of 5-HT production to a normally insensitive C. elegans homolog, OCR-4, but this chimeric channel does not respond to diacetyl stimuli. Furthermore, expression of either the mouse or human TRPV2 gene under the ocr-2 promoter can substantially restore 5-HT biosynthesis in ocr-2-null mutants but cannot improve the deficits in osmotic or olfactory sensation, suggesting that TRPV2 can substitute for the role of OCR-2 only in serotonergic neurons. Thus, different sensory functions of OCR-2 arise from separable intrinsic determinants, and specific functional properties of TRPV channel proteins may be selectively conserved across phyla.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Sokolchik
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tanabe
authors.forename: Pierre F
authors.initials: PF
authors.lastname: Baldi
authors.forename: Ji Ying
authors.initials: JY
authors.lastname: Sze
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D017089:Ankyrin Repeat; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000502:physiology*; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology; D017124:Conserved Sequence; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology*; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D011993:Recombinant Fusion Proteins; D012677:Sensation / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis
chemical_list: D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; C464590:OCR-2 protein, C elegans; C108820:OSM-9 protein, C elegans; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D050051:Transient Receptor Potential Channels; C485717:Trpv2 protein, mouse; D012701:Serotonin; D014365:Tryptophan Hydroxylase