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

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.