Movatterモバイル変換

[0]ホーム
URL:

Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Nature
  • Review Article
  • Published:

TRP channels as cellular sensors

Naturevolume 426, pages517–524 (2003)Cite this article

Abstract

TRP channels are the vanguard of our sensory systems, responding to temperature, touch, pain, osmolarity, pheromones, taste and other stimuli. But their role is much broader than classical sensory transduction. They are an ancient sensory apparatus for the cell, not just the multicellular organism, and they have been adapted to respond to all manner of stimuli, from both within and outside the cell.

This is a preview of subscription content,access via your institution

Access options

Access through your institution

Subscription info for Japanese customers

We have a dedicated website for our Japanese customers. Please go tonatureasia.com to subscribe to this journal.

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

￥ 4,980

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mammalian TRP family tree.
Figure 2: Representative transmembrane currents flowing in response to a set voltage (I–V relation) of various TRP channels.
Figure 3: Three theories of store-operated Ca2+ entry.

Similar content being viewed by others

References

  1. Hille, B.Ion Channels of Excitable Membranes 3rd edn, 663–723 (Sinauer, Sunderland, MA, 2001)

    Google Scholar 

  2. Minke, B.Drosophila mutant with a transducer defect.Biophys. Struct. Mech.3, 59–64 (1977)

    CAS PubMed  Google Scholar 

  3. Montell, C., Jones, K., Hafen, E. & Rubin, G. Rescue of theDrosophila phototransduction mutation trp by germline transformation.Science230, 1040–1043 (1985)

    ADS CAS PubMed  Google Scholar 

  4. Denis, V. & Cyert, M. S. Internal Ca2+ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue.J. Cell Biol.156, 29–34 (2002)

    CAS PubMed PubMed Central  Google Scholar 

  5. Zhou, X. L. et al. The transient receptor potential channel on the yeast vacuole is mechanosensitive.Proc. Natl Acad. Sci. USA100, 7105–7110 (2003)

    ADS CAS PubMed PubMed Central  Google Scholar 

  6. de Bono, M., Tobin, D. M., Davis, M. W., Avery, L. & Bargmann, C. I. Social feeding inCaenorhabditis elegans is induced by neurons that detect aversive stimuli.Nature419, 899–903 (2002)

    ADS CAS PubMed PubMed Central  Google Scholar 

  7. Stowers, L., Holy, T. E., Meister, M., Dulac, C. & Koentges, G. Loss of sex discrimination and male–male aggression in mice deficient for TRP2.Science295, 1493–1500 (2002)

    ADS CAS PubMed  Google Scholar 

  8. Zhang, Y. et al. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways.Cell112, 293–301 (2003)

    CAS PubMed  Google Scholar 

  9. Harteneck, C., Plant, T. D. & Schultz, G. From worm to man: three subfamilies of TRP channels.Trends Neurosci.23, 159–166 (2000)

    CAS PubMed  Google Scholar 

  10. Clapham, D. E., Runnels, L. W. & Struebing, C. The TRP ion channel family.Nature Rev. Neurosci.2, 387–396 (2001)

    CAS  Google Scholar 

  11. Minke, B. & Cook, B. TRP channel proteins and signal transduction.Physiol. Rev.82, 429–472 (2002)

    CAS PubMed  Google Scholar 

  12. Montell, C., Birnbaumer, L. & Flockerzi, V. The TRP channels, a remarkably functional family.Cell108, 595–598 (2002)

    CAS PubMed  Google Scholar 

  13. Birnbaumer, L., Yidirim, E. & Abramowitz, J. A comparison of the genes coding for canonical TRP channels and their M, V and P relatives.Cell Calcium33, 419–432 (2003)

    CAS PubMed  Google Scholar 

  14. Nilius, B. TRP Channels: facts, fiction, challenges.Cell Calcium14, 33–34 (2003)

    Google Scholar 

  15. Corey, D. New TRP channels in hearing and mechanosensation.Neuron39, 585–588 (2003)

    CAS PubMed  Google Scholar 

  16. Wes, P. D. et al. TRPC1, a human homolog of aDrosophila store-operated channel.Proc. Natl Acad. Sci. USA92, 9652–9656 (1995)

    ADS CAS PubMed PubMed Central  Google Scholar 

  17. Greka, A., Navarro, B., Oancea, E., Duggan, A. & Clapham, D. E. TRPC5 is a regulator of hippocampal neurite length and growth cone morphology.Nature Neurosci.6, 837–845 (2003)

    CAS PubMed  Google Scholar 

  18. Freichel, M. et al. Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-/- mice.Nature Cell Biol.3, 121–127 (2001)

    CAS PubMed  Google Scholar 

  19. Tiruppathi, C. et al. Impairment of store-operated Ca2+ entry in TRPC4-/- mice interferes with increase in lung microvascular permeability.Circ. Res.91, 70–76 (2002)

    CAS PubMed  Google Scholar 

  20. Zitt, C. et al. Expression of TRPC3 in Chinese hamster ovary cells results in calcium-activated cation currents not related to store depletion.J. Cell Biol.138, 1333–1341 (1997)

    CAS PubMed PubMed Central  Google Scholar 

  21. Trebak, M., Vazquez, G., Bird, G. S. & Putney, J. W. The TRPC3/6/7 subfamily of cation channels.Cell Calcium33, 451–461 (2003)

    CAS PubMed  Google Scholar 

  22. Inoue, R. et al. The transient receptor potential protein homologue TRP6 is the essential component of vascular α1-adrenoceptor-activated Ca2+-permeable cation channel.Circ. Res.88, 325–332 (2001)

    CAS PubMed  Google Scholar 

  23. Liman, E. R., Corey, D. P. & Dulac, C. TRP2: a candidate transduction channel for mammalian pheromone sensory signaling.Proc. Natl Acad. Sci. USA96, 5791–5796 (1999)

    ADS CAS PubMed PubMed Central  Google Scholar 

  24. Caterina, M. J. et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway.Nature389, 816–824 (1997)

    ADS CAS PubMed  Google Scholar 

  25. Jordt, S. E. & Julius, D. Molecular basis for species-specific sensitivity to “hot” chili peppers.Cell108, 421–430 (2002)

    CAS PubMed  Google Scholar 

  26. Chuang, H. H. et al. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.Nature411, 957–962 (2001)

    ADS CAS PubMed  Google Scholar 

  27. Caterina, M. J. et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor.Science288, 306–313 (2000)

    ADS CAS PubMed  Google Scholar 

  28. Birder, L. A. et al. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1.Nature Neurosci.5, 856–860 (2002)

    CAS PubMed  Google Scholar 

  29. Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J. & Julius, D. A capsaicin-receptor homologue with a high threshold for noxious heat.Nature398, 436–441 (1999)

    ADS CAS PubMed  Google Scholar 

  30. Kanzaki, M. et al. Translocation of a calcium-permeable cation channel induced by insulin-like growth factor-I.Nature Cell Biol.1, 165–170 (1999)

    CAS PubMed  Google Scholar 

  31. Iwata, Y. et al. A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel.J. Cell Biol.161, 957–967 (2003)

    CAS PubMed PubMed Central  Google Scholar 

  32. Smith, G. D. et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein.Nature418, 186–190 (2002)

    ADS CAS PubMed  Google Scholar 

  33. Xu, H. et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel.Nature418, 181–186 (2002)

    ADS CAS PubMed  Google Scholar 

  34. Peier, A. M. et al. A heat-sensitive TRP channel expressed in keratinocytes.Science296, 2046–2049 (2002)

    ADS CAS PubMed  Google Scholar 

  35. Guler, A. D. et al. Heat-evoked activation of the ion channel, TRPV4.J. Neurosci.22, 6408–6414 (2002)

    CAS PubMed PubMed Central  Google Scholar 

  36. Benham, C. D., Gunthorpe, M. J. & Davis, J. B. TRPV channels as temperature sensors.Cell Calcium33, 479–487 (2003)

    CAS PubMed  Google Scholar 

  37. Strotmann, R., Harteneck, C., Nunnenmacher, K., Schultz, G. & Plant, T. D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity.Nature Cell Biol.2, 695–702 (2000)

    CAS PubMed  Google Scholar 

  38. Liedtke, W. et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.Cell103, 525–535 (2000)

    CAS PubMed PubMed Central  Google Scholar 

  39. Mizuno, A., Matsumoto, N., Imai, M. & Suzuki, M. Impaired osmotic sensation in mice lacking TRPV4.Am. J. Physiol. Cell Physiol.285, C96–C101 (2003)

    CAS PubMed  Google Scholar 

  40. Alessandri-Haber, N. et al. Hypotonicity induces TRPV4-mediated nociception in rat.Neuron39, 497–511 (2003)

    CAS PubMed  Google Scholar 

  41. Watanabe, H. et al. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels.Nature424, 434–438 (2003)

    ADS CAS PubMed  Google Scholar 

  42. Yue, L., Peng, J. B., Hediger, M. A. & Clapham, D. E. CaT1 manifests the pore properties of the calcium-release-activated calcium channel.Nature410, 705–709 (2001)

    ADS CAS PubMed  Google Scholar 

  43. den Dekker, E., Hoenderop, J. G., Nilius, B. & Bindels, R. J. The epithelial calcium channels, TRPV5 and TRPV6: from identification towards regulation.Cell Calcium33, 497–507 (2003)

    CAS PubMed  Google Scholar 

  44. Hoenderop, J. G. et al. Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6.EMBO J.22, 776–785 (2003)

    CAS PubMed PubMed Central  Google Scholar 

  45. Voets, T., Janssens, A., Prenen, J., Droogmans, G. & Nilius, B. Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6.J. Gen. Physiol.121, 245–260 (2003)

    CAS PubMed PubMed Central  Google Scholar 

  46. Duncan, L. M. et al. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis.Cancer Res.58, 1515–1520 (1998)

    CAS PubMed  Google Scholar 

  47. Nagamine, K. et al. Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain.Genomics54, 124–131 (1998)

    CAS PubMed  Google Scholar 

  48. Perraud, A. L. et al. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology.Nature411, 595–599 (2001)

    ADS CAS PubMed  Google Scholar 

  49. Sano, Y. et al. Immunocyte Ca2+ influx system mediated by LTRPC2.Science293, 1327–1330 (2001)

    ADS CAS PubMed  Google Scholar 

  50. Rafty, L. A., Schmidt, M. T., Perraud, A. L., Scharenberg, A. M. & Denu, J. M. Analysis ofO-acetyl-ADP-ribose as a target for Nudix ADP-ribose hydrolases.J. Biol. Chem.277, 47114–47122 (2002)

    CAS PubMed  Google Scholar 

  51. Perraud, A. L., Schmitz, C. & Scharenberg, A. M. TRPM2 Ca2+ permeable cation channels: from gene to biological function.Cell Calcium33, 519–531 (2003)

    CAS PubMed  Google Scholar 

  52. Hara, Y. et al. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death.Mol. Cell9, 163–173 (2002)

    CAS PubMed  Google Scholar 

  53. Heiner, I., Eisfeld, J. & Luckhoff, A. Role and regulation of TRP channels in neutrophil granulocytes.Cell Calcium33, 533–540 (2003)

    CAS PubMed  Google Scholar 

  54. Grimm, C., Kraft, R., Sauerbruch, S., Schultz, G. & Harteneck, C. Molecular and functional characterization of the melastatin-related cation channel TRPM3.J. Biol. Chem.278, 21493–21501 (2003)

    CAS PubMed  Google Scholar 

  55. Lee, N. et al. Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).J. Biol. Chem.278, 20890–20897 (2003)

    CAS PubMed  Google Scholar 

  56. Launay, P. et al. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.Cell109, 397–407 (2002)

    CAS PubMed  Google Scholar 

  57. Hofmann, T., Chubanov, V., Gudermann, T. & Montell, C. TRPM5 is a voltage-modulated and Ca2+-activated monovalent selective cation channel.Curr. Biol.13, 1153–1158 (2003)

    CAS PubMed  Google Scholar 

  58. Nilius, B. et al. Voltage dependence of the Ca2+ activated cation channel TRPM4.J. Biol. Chem.33, 30813–30820 (2003)

    Google Scholar 

  59. Perez, C. A. et al. A transient receptor potential channel expressed in taste receptor cells.Nature Neurosci.5, 1169–1176 (2002)

    CAS PubMed  Google Scholar 

  60. Runnels, L. W., Yue, L. & Clapham, D. E. TRP-PLIK, a bifunctional protein with kinase and ion channel activities.Science291, 1043–1047 (2001)

    ADS CAS PubMed  Google Scholar 

  61. Nadler, M. J. et al. LTRPC7 is a Mg·ATP-regulated divalent cation channel required for cell viability.Nature411, 590–595 (2001)

    ADS CAS PubMed  Google Scholar 

  62. Runnels, L. W., Yue, L. & Clapham, D. E. The TRPM7 channel is inactivated by PIP2 hydrolysis.Nature Cell Biol.4, 329–336 (2002)

    CAS PubMed  Google Scholar 

  63. Schmitz, C. et al. Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7.Cell114, 191–200 (2003)

    CAS PubMed  Google Scholar 

  64. Yamaguchi, H., Matsushita, M., Nairn, A. C. & Kuriyan, J. Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity.Mol. Cell7, 1047–1057 (2001)

    CAS PubMed  Google Scholar 

  65. McKemy, D. D., Neuhausser, W. M. & Julius, D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation.Nature416, 52–58 (2002)

    ADS CAS PubMed  Google Scholar 

  66. Peier, A. M. et al. A TRP channel that senses cold stimuli and menthol.Cell108, 705–715 (2002)

    CAS PubMed  Google Scholar 

  67. Tracey, W. D. Jr, Wilson, R. I., Laurent, G. & Benzer, S.painless, aDrosophila gene essential for nociception.Cell113, 261–273 (2003)

    CAS PubMed  Google Scholar 

  68. Story, G. M. et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.Cell112, 819–829 (2003)

    CAS PubMed  Google Scholar 

  69. Viswanath, V. et al. Opposite thermosensor in fruitfly and mouse.Nature423, 822–823 (2003)

    ADS CAS PubMed  Google Scholar 

  70. Hanaoka, K. et al. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents.Nature408, 990–994 (2000)

    ADS CAS PubMed  Google Scholar 

  71. Wu, G. et al. Somatic inactivation of Pkd2 results in polycystic kidney disease.Cell93, 177–188 (1998)

    CAS PubMed  Google Scholar 

  72. Boulter, C. et al. Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of thePkd1 gene.Proc. Natl Acad. Sci. USA98, 12174–12179 (2001)

    ADS CAS PubMed PubMed Central  Google Scholar 

  73. Nomura, H. et al. Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects.J. Biol. Chem.273, 25967–25973 (1998)

    CAS PubMed  Google Scholar 

  74. Nonaka, S., Shiratori, H., Saijoh, Y. & Hamada, H. Determination of left–right patterning of the mouse embryo by artificial nodal flow.Nature418, 96–99 (2002)

    ADS CAS PubMed  Google Scholar 

  75. Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells.Nature Genet.33, 129–137 (2003)

    CAS PubMed  Google Scholar 

  76. Sun, M. et al. Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.Hum. Mol. Genet.9, 2471–2478 (2000)

    CAS PubMed  Google Scholar 

  77. Hersh, B. M., Hartwieg, E. & Horvitz, H. R. TheCaenorhabditis elegans mucolipin-like genecup-5 is essential for viability and regulates lysosomes in multiple cell types.Proc. Natl Acad. Sci. USA99, 4355–4360 (2002)

    ADS CAS PubMed PubMed Central  Google Scholar 

  78. Di Palma, F. et al. Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice.Proc. Natl Acad. Sci. USA99, 14994–14999 (2002)

    ADS CAS PubMed PubMed Central  Google Scholar 

  79. Hilgemann, D. W., Feng, S. & Nasuhoglu, C. The complex and intriguing lives of PIP2 with ion channels and transporters.Sci. STKE2001, RE19 (2001)

    CAS PubMed  Google Scholar 

  80. Hardie, R. C. Regulation of TRP channels via lipid second messengers.Annu. Rev. Physiol.65, 735–759 (2003)

    CAS PubMed  Google Scholar 

  81. Prescott, E. D. & Julius, D. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity.Science300, 1284–1288 (2003)

    ADS CAS PubMed  Google Scholar 

  82. McLaughlin, S., Wang, J., Gambhir, A. & Murray, D. PIP2 and proteins: interactions, organization, and information flow.Annu. Rev. Biophys. Biomol. Struct.31, 151–175 (2002)

    CAS PubMed  Google Scholar 

  83. Putney, J. W. Jr & McKay, R. R. Capacitative calcium entry channels.Bioessays21, 38–46 (1999)

    PubMed  Google Scholar 

  84. Putney, J. W. Jr TRP, inositol 1,4,5-trisphosphate receptors, and capacitative calcium entry.Proc. Natl Acad. Sci. USA96, 14669–14671 (1999)

    ADS CAS PubMed PubMed Central  Google Scholar 

  85. Prakriya, M. & Lewis, R. S. CRAC channels: activation, permeation, and the search for a molecular identity.Cell Calcium33, 311–321 (2003)

    CAS PubMed  Google Scholar 

  86. Cui, J., Bian, J. S., Kagan, A. & McDonald, T. V. CaT1 contributes to the stores-operated calcium current in Jurkat T-lymphocytes.J. Biol. Chem.277, 47175–47183 (2002)

    CAS PubMed  Google Scholar 

  87. Voets, T. et al. CaT1 and the calcium release-activated calcium channel manifest distinct pore properties.J. Biol. Chem.276, 47767–47770 (2001)

    CAS PubMed  Google Scholar 

  88. Vaca, L. & Sampieri, A. Calmodulin modulates the delay period between release of calcium from internal stores and activation of calcium influx via endogenous TRP1 channels.J. Biol. Chem.277, 42178–42187 (2002)

    CAS PubMed  Google Scholar 

  89. Patterson, R. L., van Rossum, D. B. & Gill, D. L. Store-operated Ca2+ entry: evidence for a secretion-like coupling model.Cell98, 487–499 (1999)

    CAS PubMed  Google Scholar 

  90. Yao, Y., Ferrer-Montiel, A. V., Montal, M. & Tsien, R. Y. Activation of store-operated Ca2+ current inXenopus oocytes requires SNAP-25 but not a diffusible messenger.Cell98, 475–485 (1999)

    CAS PubMed  Google Scholar 

  91. Goel, M., Sinkins, W. G. & Schilling, W. P. Selective association of TRPC channel subunits in rat brain synaptosomes.J. Biol. Chem.277, 48303–48310 (2002)

    CAS PubMed  Google Scholar 

  92. Xu, X. Z. & Sternberg, P. W. AC. elegans sperm TRP protein required for sperm–egg interactions during fertilization.Cell114, 285–297 (2003)

    CAS PubMed  Google Scholar 

  93. Block, S. M. Biophysical principles of sensory transduction.Soc. Gen. Physiol. Ser.47, 1–17 (1992)

    ADS CAS PubMed  Google Scholar 

  94. Sukharev, S. I., Sigurdson, W. J., Kung, C. & Sachs, F. Energetic and spatial parameters for gating of the bacterial large conductance mechanosensitive channel, MscL.J. Gen. Physiol.113, 525–540 (1999)

    CAS PubMed PubMed Central  Google Scholar 

  95. Howard, J., Roberts, W. M. & Hudspeth, A. J. Mechanoelectrical transduction by hair cells.Annu. Rev. Biophys. Biophys. Chem.17, 99–124 (1988)

    CAS PubMed  Google Scholar 

  96. Kim, J. et al. A TRPV family ion channel required for hearing inDrosophila.Nature424, 81–84 (2003)

    ADS CAS PubMed  Google Scholar 

  97. Yellen, G. The voltage-gated potassium channels and their relatives.Nature419, 35–42 (2002)

    ADS CAS PubMed  Google Scholar 

  98. Hardie, R. C. et al. Molecular basis of amplification inDrosophila phototransduction: roles for G protein, phospholipase C, and diacylglycerol kinase.Neuron36, 689–701 (2002)

    CAS PubMed  Google Scholar 

Download references

Acknowledgements

I thank the members of the Clapham laboratory (especially H. Xu), S. McLaughlin, R. Lewis, D. Corey and C. Miller for helpful discussions, and S. Kaczmarek for artwork.

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, Pediatric Cardiology, Children's Hospital of Boston, Department of Neurobiology, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Children's Hospital, Boston, Massachusetts, 02115, USA

    David E. Clapham

Authors
  1. David E. Clapham

Corresponding author

Correspondence toDavid E. Clapham.

Ethics declarations

Competing interests

The author declares that he has no competing financial interests.

Rights and permissions

This article is cited by

Access through your institution
Buy or subscribe

Associated content

Collection

Nobel Prize in Physiology or Medicine 2021

Focus

Sensory Transduction

Advertisement

Search

Advanced search

Quick links

Nature Briefing

Sign up for theNature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox.Sign up for Nature Briefing
[8]ページ先頭
©2009-2026 Movatter.jp