Caenorhabditis elegansTRPV ion channel regulates 5HT biosynthesis in chemosensory neurons

Abstract

Serotonin (5HT) is a pivotal signaling molecule that modulates behavioral and endocrine responses to diverse chemical and physical stimuli. We report cell-specific regulation of 5HT biosynthesis by transient receptor potential V(TRPV) ion channels in C. elegans. Mutations in the TRPV genes osm-9 or ocr-2 dramatically downregulate the expression of the gene encoding the 5HT synthesis enzyme tryptophan hydroxylase(tph-1) in the serotonergic chemosensory neurons ADF, but neither the mutation nor the double mutation of both channel genes affects other types of serotonergic neurons. The TRPV genes are expressed in the ADF neurons but not in other serotonergic neurons, and act cell-autonomously to regulate a neuron-specific transcription program. Whereas in olfactory neurons OSM-9 and OCR-2 function is dependent on ODR-3 Gα, the activity of ODR-3 or two other Gα proteins expressed in the ADF neurons is not required for upregulating tph-1 expression, thus the TRPV ion channels in different neurons may be regulated by different mechanisms. A gain-of-function mutation in CaMKII UNC-43 partially suppresses the downregulation of tph-1 in the TRPV mutants, thus CaMKII may be an effector of the TRPV signaling. Mutations in the TRPV genes cause worms developmentally arrest at the Dauer stage. This developmental defect is due in part to reduced 5HT inputs into daf-2/insulin neuroendocrine signaling.

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.…”

Polymodal Sensory Function of theCaenorhabditis elegansOCR-2 Channel Arises from Distinct Intrinsic Determinants within the Protein and Is Selectively Conserved in Mammalian TRPV Proteins

“…The functions of the TRPV channel encoded by the Caenorhabditis elegans ocr-2 and osm-9 genes in chemosensory neurons have been studied genetically (Colbert et al, 1997;de Bono et al, 2002;Tobin et al, 2002;Zhang et al, 2004). ocr-2 and osm-9 are coexpressed in four pairs of chemosensory neurons: the ADF serotonergic chemosensory neurons, the AWA olfactory neurons, the ASH osmotic sensory neurons, and the ADL chemosensory neurons .…”

“…Both OSM-9 and OCR-2 are localized to the cilia, as well as to the plasma membrane . Null mutations in either ocr-2 or osm-9 cause downregulation of the expression of the tph-1 gene, which encodes the key serotonin (5-HT) biosynthetic enzyme tryptophan hydroxylase, in the ADF neurons (Zhang et al, 2004), and the odr-10 gene, which encodes a receptor for the odorant diacetyl (Sengupta et al, 1996), in the AWA neurons . Both OCR-2 and OSM-9 also are required for ASH-mediated osmotic sensation and ASH-and ADL-mediated olfactory avoidance (Colbert et al, 1997;Tobin et al, 2002); however, several efforts have not been able to identify an effect of the activity of this channel on the expression of sensory components in ASH and ADL (I. Sokolchik and J. Sze, unpublished observations).…”

“…Previous studies imply that the OCR-2/OSM-9 TRPV channel regulates different sensory functions via distinct signaling transduction pathways (Zhang et al, 2004). The odr-3 gene encodes a G␣-protein and is expressed in all ocr-2-expressing amphid chemosensory neurons.…”

“…ODR-3 is an essential component for the OCR-2/OSM-9 channel to mediate the olfactory and osmotic sensation (Colbert et al, 1997;Roayaie et al, 1998;Tobin et al, 2002). However, ocr-2-and osm-9-dependent transcriptional regulation of tph-1 expression in the ADF neurons is unaffected by deletion mutations in odr-3 or two other G␣-proteins expressed in ADF (Zhang et al, 2004). Furthermore, the ASH neurons mediate osmotic sensation as well as social behavior, and both responses are dependent on OCR-2 and OSM-9; only osmotic sensation, not the social behavior, requires ODR-3 (de Bono et al, 2002).…”