A Heat-Sensitive TRP Channel Expressed in Keratinocytes

Peier, Andrea; Reeve, Alya; Andersson, David A.; Moqrich, Aziz; Earley, Taryn J.; Hergarden, Anne C.; Story, Gina M.; Colley, Sian; Hogenesch, John B.; McIntyre, Peter; Bevan, Stuart; Patapoutian, Ardem

doi:10.1126/science.1073140

Cited by 838 publications

(780 citation statements)

References 20 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: 54%

“…Therefore, the actual temperature threshold for TRPV3 expressed in Xenopus oocytes remains undermined. Since the heat response of TRPV3 expressed in oocytes is greatly enhanced in the presence of 2APB [15] and it is clearly detectable by whole-cell patch clamp recording in the absence of 2APB when the same channel is expressed in CHO and HEK 293 cells [4,18], it is possible that the temperature threshold of TRPV3 in oocytes is slightly higher than those determined in mammalian cells (33-39 °C). However, the large endogenous response to heat of higher than 40 °C makes this measurement very difficult.…”

Section: Altered Temperature Response Of the G573 Mutants Expressed Imentioning

confidence: 99%

“…Amongst all mammalian TRP channels, only TRPV3 and TRPV4 have been shown to be highly expressed and functional in skin keratinocytes [4][5][6][7][8]. Most studies have focused on the sensory functions of these channels, primarily the sensation of warm and hot temperatures.…”

Section: Introductionmentioning

confidence: 99%

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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: 54%

Section: Altered Temperature Response Of the G573 Mutants Expressed Imentioning

confidence: 99%

See 1 more Smart Citation

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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show abstract

“…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%

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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Thermosensation

Mak

Zhang

McNaughton

2009

Encyclopedia of Life Sciences

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Detection of temperature, both of the surroundings and of the body itself, is critical for maintaining normal physiological functioning. To date, a number of thermo‐sensitive ion channels have been reported to be involved in thermosensation, six of which belong to the transient receptor potential (TRP) superfamily of nonselective cation channels. Each of these operates over a distinct temperature range and many respond to natural compounds that elicit sensations of heat or cold. The best studied is TRP vanilloid 1 (TRPV1), which is both a receptor for capsaicin, the active principle of chilli peppers, and a painful heat receptor which responds to temperatures over 42°C. Our understanding of cold transduction has also rapidly increased in recent years with the intriguing discovery of the cold receptors TRP melastatin 8 (TRPM8) and TRP ankyrin 1 (TRPA1). Key concepts Our current understanding of thermosensation comes mainly from the identification of six temperature‐sensitive ion channels (thermo‐TRP channels) belonging to the transient receptor potential (TRP) superfamily of nonselective calcium channels. Each thermo‐TRP operates over a distinct temperature range. Four of them (TRPV1–4) are activated by heat, and two of them (TRPM8 and TRPA1) are activated by cold. Thermo‐TRPs also respond to natural compounds that elicit corresponding psychophysical sensations of heat or cold. The response of these channels is regulated after tissue damage and is subjected to modulation by inflammatory mediators released at the site of injury. The altered sensitivity of these channels accounts for the phenomenon of thermal hyperalgesia. Inflammatory mediators sensitize TRPV1 via the activation of protein kinases such as protein kinase C (PKC), protein kinase A (PKA) and Src. The modulation of TRPV1 by PKC and PKA depends on the correct positioning of the kinases by a scaffolding protein, AKAP79/150. There are other possible mechanisms involved in thermosensation, for example, modulation of potassium channels such as TREK‐2.

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A Heat-Sensitive TRP Channel Expressed in Keratinocytes

Cited by 838 publications

References 20 publications

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

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

Temperature sensing across species

Thermosensation

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