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The Journal of Physiological Sciences

, Volume 66, Issue 5, pp 359–365 | Cite as

Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor

  • Koji Shibasaki
Review

Abstract

This review provides a summary of the physiological significance of the TRPV2 ion channel. While TRPV2 was initially characterized as a noxious heat sensor, we found that TRPV2 can also act as a mechanosensor in embryonic neurons or adult myenteric neurons. Here, we summarize the newly characterized functions of TRPV2, including the research progress that has been made toward our understanding of TRPV2 physiology, and discuss other recent data pertaining to TRPV2. It is thought that TRPV2 may be an important drug target based on its broad expression patterns and important physiological roles. The possible associations between diseases and TRPV2 are also discussed.

Keywords

TRPV2 Mechanical stimulus Axon outgrowth Mechanosensor Thermosensor 

Notes

Acknowledgments

The author would like to acknowledge the following funding sources: Grants-in-Aid for Scientific Research (KAKENHI Project No. 15H05934 <Thermal Biology>, 21200012, 20399554, 24111507 + 26111702 <Brain Environment>, 26117502 <glial assembly>, 15H03000) from the Ministry of Education, Culture, Sports, Science and Technology, Japan; a grant from Uehara Memorial Foundation; a grant from Takeda Science Foundation, Tokyo, Japan; a grant from the Sumitomo Foundation; a grant from the Brain Science Foundation; a grant from Narishige Neuroscience Research Foundation; a grant from Salt Science Research Foundation No.14C2; and a grant from the Ichiro Kanehara Foundation.

References

  1. 1.
    Minke B (1977) Drosophila mutant with a transducer defect. Biophys Struct Mech 3:59–64CrossRefPubMedGoogle Scholar
  2. 2.
    Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323CrossRefPubMedGoogle Scholar
  3. 3.
    Tominaga M, Caterina MJ (2004) Thermosensation and pain. J Neurobiol 61:3–12CrossRefPubMedGoogle Scholar
  4. 4.
    Levine JD, Alessandri-Haber N (2007) TRP channels: targets for the relief of pain. Biochim Biophys Acta 1772:989–1003CrossRefPubMedGoogle Scholar
  5. 5.
    Chung MK, Jung SJ, Oh SB (2011) Role of TRP channels in pain sensation. Adv Exp Med Biol 704:615–636CrossRefPubMedGoogle Scholar
  6. 6.
    Cao E, Liao M, Cheng Y, Julius D (2013) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504:113–118CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D (2015) Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 520:511–517CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Nilius B (2007) TRP channels in disease. Biochim Biophys Acta 1772:805–812CrossRefPubMedGoogle Scholar
  9. 9.
    Peralvarez-Marin A, Donate-Macian P, Gaudet R (2013) What do we know about the transient receptor potential vanilloid 2 (TRPV2) ion channel? FEBS J 280:5471–5487CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Fleig A, Penner R (2004) The TRPM ion channel subfamily: molecular, biophysical and functional features. Trends Pharmacol Sci 25:633–639CrossRefPubMedGoogle Scholar
  11. 11.
    Colbert HA, Smith TL, Bargmann CI (1997) OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans. J Neurosci Off J Soc Neurosci 17:8259–8269Google Scholar
  12. 12.
    Kim J, Chung YD, Park DY, Choi S, Shin DW et al (2003) A TRPV family ion channel required for hearing in Drosophila. Nature 424:81–84CrossRefPubMedGoogle Scholar
  13. 13.
    Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD et al (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824CrossRefPubMedGoogle Scholar
  14. 14.
    Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H et al (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543CrossRefPubMedGoogle Scholar
  15. 15.
    Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J et al (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313CrossRefPubMedGoogle Scholar
  16. 16.
    Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398:436–441CrossRefPubMedGoogle Scholar
  17. 17.
    Kanzaki M, Zhang YQ, Mashima H, Li L, Shibata H et al (1999) Translocation of a calcium-permeable cation channel induced by insulin-like growth factor-I. Nat Cell Biol 1:165–170CrossRefPubMedGoogle Scholar
  18. 18.
    Jin X, Touhey J, Gaudet R (2006) Structure of the N-terminal ankyrin repeat domain of the TRPV2 ion channel. J Biol Chem 281:25006–25010CrossRefPubMedGoogle Scholar
  19. 19.
    Cohen MR, Huynh KW, Cawley D, Moiseenkova-Bell VY (2013) Understanding the cellular function of TRPV2 channel through generation of specific monoclonal antibodies. PLoS One 8:e85392CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Park U, Vastani N, Guan Y, Raja SN, Koltzenburg M et al (2011) TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception. J Neurosci Off J Soc Neurosci 31:11425–11436CrossRefGoogle Scholar
  21. 21.
    Shibasaki K, Murayama N, Ono K, Ishizaki Y, Tominaga M (2010) TRPV2 enhances axon outgrowth through its activation by membrane stretch in developing sensory and motor neurons. J Neurosci Off J Soc Neurosci 30:4601–4612CrossRefGoogle Scholar
  22. 22.
    Mihara H, Boudaka A, Shibasaki K, Yamanaka A, Sugiyama T et al (2010) Involvement of TRPV2 activation in intestinal movement through nitric oxide production in mice. J Neurosci Off J Soc Neurosci 30:16536–16544CrossRefGoogle Scholar
  23. 23.
    Shibasaki K, Ishizaki Y, Mandadi S (2013) Astrocytes express functional TRPV2 ion channels. Biochem Biophys Res Commun 441:327–332CrossRefPubMedGoogle Scholar
  24. 24.
    Muraki K, Iwata Y, Katanosaka Y, Ito T, Ohya S et al (2003) TRPV2 is a component of osmotically sensitive cation channels in murine aortic myocytes. Circ Res 93:829–838CrossRefPubMedGoogle Scholar
  25. 25.
    Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K et al (2009) The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. J Biol Chem 284:21257–21264CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Cohen MR, Johnson WM, Pilat JM, Kiselar J, DeFrancesco-Lisowitz A et al (2015) Nerve growth factor regulates transient receptor potential vanilloid 2 via extracellular signal-regulated kinase signaling to enhance neurite outgrowth in developing neurons. Mol Cell Biol 35:4238–4252PubMedPubMedCentralGoogle Scholar
  27. 27.
    Kettenmann H, Ransom BR (eds) (2005) Neuroglia, 3rd edn. Oxford University Press, New York, pp 135–148Google Scholar
  28. 28.
    Takano T, Tian GF, Peng W, Lou N, Libionka W et al (2006) Astrocyte-mediated control of cerebral blood flow. Nat Neurosci 9:260–267CrossRefPubMedGoogle Scholar
  29. 29.
    Mulligan SJ, MacVicar BA (2004) Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431:195–199CrossRefPubMedGoogle Scholar
  30. 30.
    Piet R, Jahr CE (2007) Glutamatergic and purinergic receptor-mediated calcium transients in Bergmann glial cells. J Neurosci 27:4027–4035CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Sakatani S, Seto-Ohshima A, Shinohara Y, Yamamoto Y, Yamamoto H et al (2008) Neural-activity-dependent release of S100B from astrocytes enhances kainate-induced gamma oscillations in vivo. J Neurosci 28:10928–10936CrossRefPubMedGoogle Scholar
  32. 32.
    Shibasaki K, Ikenaka K, Tamalu F, Tominaga M, Ishizaki Y (2014) A novel subtype of astrocytes expressing TRPV4 (transient receptor potential vanilloid 4) regulates neuronal excitability via release of gliotransmitters. J Biol Chem 289:14470–14480CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Shibasaki K, Sugio S, Takao K, Yamanaka A, Miyakawa T et al (2015) TRPV4 activation at the physiological temperature is a critical determinant of neuronal excitability and behavior. Pflugers Arch 467:2495–2507CrossRefPubMedGoogle Scholar
  34. 34.
    Shibasaki K, Suzuki M, Mizuno A, Tominaga M (2007) Effects of body temperature on neural activity in the hippocampus: regulation of resting membrane potentials by transient receptor potential vanilloid 4. J Neurosci 27:1566–1575CrossRefPubMedGoogle Scholar
  35. 35.
    Hassan S, Eldeeb K, Millns PJ, Bennett AJ, Alexander SP et al (2014) Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br J Pharmacol 171:2426–2439CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Link TM, Park U, Vonakis BM, Raben DM, Soloski MJ et al (2010) TRPV2 has a pivotal role in macrophage particle binding and phagocytosis. Nat Immunol 11:232–239CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Nagasawa M, Nakagawa Y, Tanaka S, Kojima I (2007) Chemotactic peptide fMetLeuPhe induces translocation of the TRPV2 channel in macrophages. J Cell Physiol 210:692–702CrossRefPubMedGoogle Scholar
  38. 38.
    Zhang D, Spielmann A, Wang L, Ding G, Huang F et al (2012) Mast-cell degranulation induced by physical stimuli involves the activation of transient-receptor-potential channel TRPV2. Physiol Res Acad Sci Bohemoslov 61:113–124Google Scholar
  39. 39.
    Stokes AJ, Shimoda LM, Koblan-Huberson M, Adra CN, Turner H (2004) A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells. J Exp Med 200:137–147CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Saunders CI, Kunde DA, Crawford A, Geraghty DP (2007) Expression of transient receptor potential vanilloid 1 (TRPV1) and 2 (TRPV2) in human peripheral blood. Mol Immunol 44:1429–1435CrossRefPubMedGoogle Scholar
  41. 41.
    Park KS, Kim Y, Lee YH, Earm YE, Ho WK (2003) Mechanosensitive cation channels in arterial smooth muscle cells are activated by diacylglycerol and inhibited by phospholipase C inhibitor. Circ Res 93:557–564CrossRefPubMedGoogle Scholar
  42. 42.
    Fantozzi I, Zhang S, Platoshyn O, Remillard CV, Cowling RT et al (2003) Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 285:L1233–L1245CrossRefPubMedGoogle Scholar
  43. 43.
    Muraki K, Iwata Y, Katanosaka Y, Ito T, Ohya S et al (2003) TRPV2 is a component of osmotically sensitive cation channels in murine aortic myocytes. Circ Res 93:829–838CrossRefPubMedGoogle Scholar
  44. 44.
    Katanosaka Y, Iwasaki K, Ujihara Y, Takatsu S, Nishitsuji K et al (2014) TRPV2 is critical for the maintenance of cardiac structure and function in mice. Nat Commun 5:3932CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G et al (2002) Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J Biol Chem 277:47044–47051CrossRefPubMedGoogle Scholar
  46. 46.
    Hisanaga E, Nagasawa M, Ueki K, Kulkarni RN, Mori M et al (2009) Regulation of calcium-permeable TRPV2 channel by insulin in pancreatic beta-cells. Diabetes 58:174–184CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Imura A, Tsuji Y, Murata M, Maeda R, Kubota K et al (2007) alpha-Klotho as a regulator of calcium homeostasis. Science 316:1615–1618CrossRefPubMedGoogle Scholar
  48. 48.
    Lin Y, Sun Z (2012) Antiaging gene Klotho enhances glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 in MIN6 beta-cells. Endocrinology 153:3029–3039CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Caprodossi S, Lucciarini R, Amantini C, Nabissi M, Canesin G et al (2008) Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage. Eur Urol 54:612–620CrossRefPubMedGoogle Scholar
  50. 50.
    Monet M, Lehen’kyi V, Gackiere F, Firlej V, Vandenberghe M et al (2010) Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res 70:1225–1235CrossRefPubMedGoogle Scholar
  51. 51.
    Alptekin M, Eroglu S, Tutar E, Sencan S, Geyik MA et al (2015) Gene expressions of TRP channels in glioblastoma multiforme and relation with survival. Tumour Biol J Int Soc Oncodevelop Biol Med 36:9209–9213CrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  1. 1.Department of Molecular and Cellular NeurobiologyGunma University Graduate School of MedicineMaebashiJapan

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