Combinatorial Expression of TRPV Channel Proteins Defines Their Sensory Functions and Subcellular Localization in C. elegans Neurons

Abstract

C. elegans OSM-9 is a TRPV channel protein involved in sensory transduction and adaptation. Here, we show that distinct sensory functions arise from different combinations of OSM-9 and related OCR TRPV proteins. Both OSM-9 and OCR-2 are essential for several forms of sensory transduction, including olfaction, osmosensation, mechanosensation, and chemosensation. In neurons that express both OSM-9 and OCR-2, tagged OCR-2 and OSM-9 proteins reside in sensory cilia and promote each other's localization to cilia. In neurons that express only OSM-9, tagged OSM-9 protein resides in the cell body and acts in sensory adaptation rather than sensory transduction. Thus, alternative combinations of TRPV proteins may direct different functions in distinct subcellular locations. Animals expressing the mammalian TRPV1 (VR1) channel in ASH nociceptor neurons avoid the TRPV1 ligand capsaicin, allowing selective, drug-inducible activation of a specific behavior.

Generation and modulation of chemosensory behaviors in C. elegans

“…Thus, the ASH, ADL, and AWB sensory neuron types, which are the primary sensors of toxic chemicals or nociceptive stimuli, synapse directly onto backward command interneurons that direct backward locomotion via activation or inhibition of motor neurons [53] (Fig. 1a), enabling the worm to execute a rapid and robust escape response when these neurons are activated [63][64][65]. On the other hand, neurons that sense attractive chemicals synapse onto intervening layers of interneurons.…”

“…Thus, in the absence of TAX-2/4 function, these neurons fail to respond to any odorants. However, in a subset of additional neuron types, primary chemosensory signal transduction is likely mediated via the OSM-9 and OCR-2 TRPV channels, which may be gated by polyunsaturated fatty acids (PUFAs) or their derivatives [63,113,144] (Fig. 2b).…”

“…As each chemosensory neuron expresses multiple chemoreceptors, alteration of expression of individual receptors provides a mechanism by which worms can selectively alter their response to a single chemical sensed by that neuron type, without altering responses to other chemicals. Indeed, individual chemoreceptor genes have been shown to be regulated by a plethora of mechanisms including neuronal activity, internal metabolic state, levels of pheromone, and intercellular signaling [25,63,100,107,108,157] (A. van der Linden, K. Kim and P.S., unpublished observations; Fig. 3a).…”

Temperature sensing across species

“…Surprisingly, the pungent component of hot chili peppers capsaicin, which activates the mammalian thermosensor TRPV1 (see below) [25], sensitized withdrawal behaviors [24]. Capsaicin itself does not evoke an acute nocifensive response, but this effect is attenuated by the competitive capsaicin antagonist capsa-zepine [24,26]. The C. elegans genome contains several capsaicin receptor-related genes of which osm-9 and ocr-2 are required for nociceptive responses mediated by the ASH nociceptor [23].…”

Structure-function analysis of TRPV channels

“…Another important mechanism of TRPV localization and targeting has been discovered in invertebrates: Here, it has been shown by an elegant study in C. elegans (Tobin et al 2002), that one function of combinatorial TRPV (OSM9, OCR 1-4) expression is to specify subcellular localization. In order to be expressed in the sensory cilia of defined neurons, OSM9 for example requires the OCR2 protein and vice versa.…”