Polymodal Sensory Function of theCaenorhabditis elegansOCR-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.

Transient receptor potential vanilloid channels functioning in transduction of osmotic stimuli

“…The reasons for this discrepancy are not understood. Related to this study, it was recently reported that TRPV2 could rescue one particular deficit of the ocr-2 mutant, namely the dramatic downregulation of serotonin biosynthesis in the sensory ADF neuron, but mammalian TRPV2, unlike TRPV4 directing behavior in osm-9, did not complement the lack of the osmotic avoidance reaction of ocr-2 (Zhang et al 2004, Sokolchik et al 2005. However, common to these two investigations is the conservation of TRPV signaling across phyla that have separated for several hundred million years of molecular evolution, despite low sequence homology.…”

Cilia and cell cycle re-entry

“…37 Interestingly, replacing the TRPV ortholog in C. elegans, OCR-2, with human or mouse TRPV2 rescued the loss of chemosensory perception and showed a localization pattern along the sensory cilia and plasma membrane. 38 It is tempting to speculate that IGF-1 stimulation in ciliated mammalian cells may utilize TRPV2 at the cilium or plasma membrane to increase intracellular Ca 2+ levels and possibly result in ciliary resorption.…”

Dependence of regulatory volume decrease on transient receptor potential vanilloid 4 (TRPV4) expression in human corneal epithelial cells

“…Many members of this superfamily are polymodally activated by a diverse assortment of environmental challenges, including osmotic, mechanical, and thermal stresses and cues [19,20]. For a variety of tissues, there is emerging evidence that regulatory volume responses are dependent on increases in Ca 2+ influx through pathways comprising several different members of the TRP superfamily [21][22][23][24].…”