TRPV3 is a calcium-permeable temperature-sensitive cation channel

Xu, Haoxing; Ramsey, I. Scott; Kotecha, Suhas A.; Moran, Magdalene M.; Chong, Jayhong A.; Lawson, D.; Ge, Pei; Lilly, Jeremiah; Silos‐Santiago, Inmaculada; Xie, Yannan; DiStefano, Peter S.; Curtis, Rory; Clapham, David E.

doi:10.1038/nature00882

Cited by 799 publications

(783 citation statements)

References 28 publications

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“…The Q10 values before and after the transition are 1.45 ± 0.15 and 3.63 ± 0.33, respectively. The temperature threshold is 15 ± 1 °C (n = 5), which is significantly lower than the published value for the wild type TRPV3 (33-39°C) expressed in mammalian cells [4,21,22]. The Q10 value of 3.6 at above 15 °C for the coexpressed oocytes indicates a moderate temperature regulation.…”

Section: Altered Temperature Response Of the G573 Mutants Expressed Imentioning

confidence: 53%

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

Xiao¹,

Tian²,

Tang³

et al. 2008

Cell Calcium

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SummaryTRPV3 is a non-selective cation channel activated by warm to hot temperatures. In rodents, TRPV3 is highly expressed in basal keratinocytes of skin and oral/nasal epithelia. TRPV3 knockout mice showed impaired responses to innocuous and noxious heat but otherwise normal appearance and reactions to many sensory modalities. However, point mutations of TRPV3 at Gly573 to Ser and Cys have recently been linked to autosomal dominant hairless phenotypes and spontaneous dermatitis in mice and rats, implicating an important role for TRPV3 in alopecia and skin diseases. Exactly how the mutations affect TRPV3 function was unexplained. Here we show that both G573S and G573C mutations of murine TRPV3 are constitutively active in heterologous systems. In HEK293 cells, expression of the TRPV3 mutants causes cell death. In Xenopus oocytes, the constitutively active mutant channel is irresponsive to thermal and chemical stimuli but it reduces the temperature threshold and enhances the responses to heat and TRPV3 agonists of the wild type channel when they are co-expressed. We conclude that the G573S and G573C substitutions render the TRPV3 channel spontaneously active under normal physiological conditions, which in turn alters ion homeostasis and membrane potentials of skin keratinocytes, leading to hair loss and dermatitis-like skin diseases.

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Section: Altered Temperature Response Of the G573 Mutants Expressed Imentioning

confidence: 53%

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

Xiao¹,

Tian²,

Tang³

et al. 2008

Cell Calcium

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“…Subsequently, we identified a cold and menthol receptor, TRPM8, from TG neurons using a similar paradigm, thereby establishing that members of the TRP family of ion channels play an important role in thermosensation [47]. Subsequently, four additional TRP channels have been implicated in temperature sensation both in vitro and in vivo, and their properties, along with TRPV1 and TRPM8, can conceivably account for the entire spectrum of perceived temperatures [48][49][50][51][52][53][54][55] (Fig. 3).…”

Section: Vertebrate Thermosensory Mechanismsmentioning

confidence: 90%

“…Hence, the cloning and functional analysis of TRPV1 revealed for the first time how sensory neurons detect "moderate" threshold heat responses at the molecular level. Furthermore, several additional TRPV channels are also activated by warmth and heat, suggesting that thermosensory responses to heat are largely mediated by one class of proteins (see below) [48][49][50][52][53][54].…”

Section: Cloning Of the Capsaicin And Menthol Receptorsmentioning

confidence: 99%

“…In vitro, TRPV3 and TRPV4 are activated at temperatures considered warm [49,50,[52][53][54]. TRPV4, a functional orthologue of the C. elegans TRP channel Osm-9 [90,91], was first identified as an osmosensitive ion channel and is activated by decreased osmolarity [92][93][94].…”

Section: Mouse Models Deficient In Temperature Sensingmentioning

confidence: 99%

“…TRPV3, alternatively, is activated by a number of natural plant products that produce a sensation of warmth, including camphor and the active components of oregano, thyme, and cloves [83,96]. Remarkably, TRPV3 appears to be exclusively expressed in keratinocytes, and ionic currents are reported to be evoked at threshold temperatures of either 31 or 39°C in heterologous cells expressing the channel [52][53][54]. Thus, these two TRPV channels were hypothesized to mediate the signaling of warm temperatures in ranges below that detected by either TRPV1 or TRPV2.…”

Section: Mouse Models Deficient In Temperature Sensingmentioning

confidence: 99%

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Temperature sensing across species

McKemy

2007

Pflugers Arch - Eur J Physiol

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The ability to detect changes in temperature is a fundamental sensory mechanism for every species and provides organisms with a detailed view of the environment. This review focuses on what is known of the neuronal and molecular substrates for thermosensation across species, focusing on the three robust model systems extensively used to study sensory signaling, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the laboratory mouse. Nematodes migrate to thermal climes that are amenable to their survival, a behavior that is regulated primarily through a single sensory neuron. Additionally, nematodes "learn" to seek out this temperate zone based upon their prior experience, a robust model of learning and memory. Drosophila larvae also prefer select thermal zones that are optimal for growth and have also developed vigorous mechanisms to avoid unfavorable conditions. In mammals, the transduction mechanisms for thermosensation have been identified primarily due to the fact that naturally occurring plant products evoke distinct psychophysical sensation of temperature change. More remarkably, the elucidation of the molecular sensors in mammals, along with those in Drosophila, has demonstrated conservation in the molecular mediators of temperature sensation across diverse species.

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