A TRP Channel that Senses Cold Stimuli and Menthol

Peier, Andrea; Moqrich, Aziz; Hergarden, Anne C.; Reeve, Alya; Andersson, David A.; Story, Gina M.; Earley, Taryn J.; Dragoni, I.; McIntyre, Peter; Bevan, Stuart; Patapoutian, Ardem

doi:10.1016/s0092-8674(02)00652-9

Cited by 2,018 publications

(1,892 citation statements)

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“…All three are specifically expressed in TrkA-positive DRG neurons in newborn mice [13][14][15] . The expression of these TrkA-specific genes was not detectable in TrkA TrkC/TrkC mice or in TrkA τlacZ/τlacZ mice ( Fig.…”

Section: The Rescued Neurons Adopt a Proprioceptive Phenotypementioning

confidence: 99%

Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate

et al. 2004

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Tactile information is perceived by a heterogeneous population of specialized neurons. Neurotrophin receptors (the receptor tyrosine kinases, Trks) mark the major classes of these sensory neurons: TrkA is expressed in neurons that sense temperature and noxious stimuli, and TrkC is expressed in proprioceptive neurons that sense body position. Neurotrophin signaling through these receptors is required for cell survival. To test whether neurotrophins have an instructive role in sensory specification, we expressed rat TrkC from the TrkA (also known as Ntrk1) locus in mice. The surviving presumptive TrkA-expressing neurons adopted a proprioceptive phenotype, indicating that neurotrophin signaling can specify sensory neuron subtypes.Neurotrophins are well-characterized growth factors required for the survival of developing sensory neurons by signaling through a class of receptor tyrosine kinases 1-3 . The Trk receptors are specifically expressed in functionally distinct neurons of the dorsal root ganglia (DRG). TrkA, the receptor for nerve growth factor (NGF) is expressed in nociceptive and thermoceptive sensory neurons; TrkC, the high-affinity receptor for neurotrophin-3 (NT-3), is expressed in proprioceptive neurons; and TrkB, the receptor for brain-derived neurotrophic factor (BDNF) and NT-4, is expressed in less specifically characterized touch neurons. Each Trk receptor is required for the survival of the distinct class of neurons that it marks, consistent with a permissive role of neurotrophin signaling in neuronal survival. Various studies have suggested that Trk signaling is also involved in instructive steps of DRG development 4 . For example, neurotrophins are able to guide DRG axons in culture, and Bax -/-; TrkA -/-or Bax -/-;NT3 -/-DRG neurons, which are rescued from apoptosis by the lack of functional Bax protein, fail to develop properly 5-10 . To directly test whether signaling by a specific Trk can specify the subtype of DRG neurons in vivo, we designed a knock-in construct that expresses rat TrkC protein from the mouse TrkA locus while inactivating native TrkA expression. Table 2 and Fig. 4e-h).To further demonstrate that an effect on survival of existing proprioceptive neurons cannot account for the phenotype observed in TrkA TrkC/TrkC mice, we crossed the knock-in mice to Bax -/-mice. The deletion of Bax rescues DRG neurons from apoptosis, but does not cause the formation of extra proprioceptive neurons, as judged by the number of muscle spindles 10 (also compare parvalbumin and spindle counts in wild-type and Bax -/-mice; Tables 1 and 2). Notably, we observed a five-fold increase in parvalbumin-positive L5 DRGs and a seven-fold increase in muscle spindles in the soleus muscle of TrkA TrkC/TrkC ;Bax -/-mice when compared to Bax -/-mice ( Functional endogenous TrkC is required for the phenotypic switchIn an attempt to visualize the projection patterns of the ectopic proprioceptive neurons, we analyzed TrkA τlacZ/TrkC compound heterozygous mice. The TrkA-positive DRG neuronal projections are...

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Section: The Rescued Neurons Adopt a Proprioceptive Phenotypementioning

confidence: 99%

Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate

et al. 2004

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“…Thus, TRPM2, TRPM3 and TRPM8 are Ca 2+ permeable nonselective cation channels, which differ substantially with respect to their activation stimuli (Chuang et al 2004;Grimm et al 2003;Hara et al 2002;Lee et al 2003;McKemy et al 2002;Peier et al 2002;Sano et al 2001;Wehage et al 2002). TRPM8 is activated by low temperature (Chuang et al 2004;Voets et al 2004a), while TRPM2 is stimulated by intracellular ADP-ribose, NAD + and oxidative stress (Hara et al 2002;Perraud et al 2001Perraud et al , 2003).…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of TRPM6/TRPM7 channel kinase signal transduction complexes

Chubanov

Schnitzler

Wäring

et al. 2005

Naunyn-Schmiedeberg's Arch Pharmacol

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Investigations into Drosophila mutants with impaired vision due to mutations in the transient receptor potential gene (trp) initiated a systematic search for TRP homologs in other species, finally leading to the discovery of a whole new family of plasma membrane cation channels involved in multiple physiological processes. Among the recently discovered TRP cation channels two homologous proteins, TRPM6 and TRPM7, display unique domain compositions and biophysical properties. These remarkable genes are vital for Mg 2+ homeostasis in vertebrates and, if disrupted, lead to cell death or human disease.

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“…Biophysically, TRPM8 has surprisingly similar properties to those recorded in both cultured DRG and TG neurons using similar experimental paradigms [47,71]. TRPM8 currents are evoked by cold with an activation threshold temperature of ~26°C, with activity increasing in magnitude down to 8°C, spanning what are considered both innocuous cool (~30-15°C) and noxious cold temperatures (<15°C) [47,51]. TRPM8 was the first cold-activated ion channel to be identified and established the general role for TRP ion channels in thermosensation.…”

Section: Cloning Of the Capsaicin And Menthol Receptorsmentioning

confidence: 75%

“…Similar to the process where a sensor for heat was found with capsaicin, we and others identified a cold sensor on sensory afferents by cloning a menthol receptor, TRPM8 [47,51]. When the channel is expressed in heterologous expression systems, currents are activated by a number of cooling compounds in addition to menthol, such as eucalyptol (the active ingredient in eucalyptus oil) and the super-cooling compound AG-3-5 [47,81].…”

Section: Cloning Of the Capsaicin And Menthol Receptorsmentioning

confidence: 80%

“…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%

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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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A TRP Channel that Senses Cold Stimuli and Menthol

Cited by 2,018 publications

References 25 publications

Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate

Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate

Emerging roles of TRPM6/TRPM7 channel kinase signal transduction complexes

Temperature sensing across species

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