My lab studies the biological functions and biophysical characteristics of a group of ion channel proteins of the Transient Receptor Potential Vanilloid (TRPV) family, TRPV1, TRPV2, TRPV3 and TRPV4. These channels share the intriguing feature that they can be activated by warm or painfully hot temperatures, as well as by many nonthermal stimuli. For example, TRPV1, the founding member of this family, can be activated by painful heat (>42°C), by protons, or by pungent chemicals such as capsaicin. This channel is strongly expressed in nociceptive neurons and is essential for normal behavioral responses to noxious heat. More recently, we made the unexpected discovery that TRPV2 is critical for the ability of macrophages to carry out phagocytosis and to protect the host from infection with pathogenic bacteria. By examining these channels in recombinant and native systems, and taking advantage of knockout mice lacking one or more subtypes, we are dissecting the biological contributions of these channels to thermosensory and nonthermosensory processes in both neuronal and nonneuronal cells.
Current areas of emphasis include:
1) Understanding the mechanisms by which TRPV1 and TRPV3 dynamically alter their selectivities among Ca2+, Na+ and other cations during persistent stimulation, and the biological significance of this plasticity
2) Understanding the mechanisms by which keratinocytes in the skin contribute to “indirect” thermosensation and pain perception by signaling to epidermal nerve endings
3) Examination of nonthermosensory roles for TRPV channels in epithelial cells of the skin and urinary bladder
4) Understanding the contribution of TRPV2 to phagocytosis and innate immune responses of macrophages and dendritic cells |
Huang SM, Li X, Yu Y, Wang J, Caterina MJ. (2011) TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation. Mol Pain. 2011 May 17;7(1):37.
PubMed Reference
Munns, C.H. and Caterina, J.R. (2011) Tune in to KCNQ. Nat Neuroscience, 2011, Dec 23; 15(1):8-10.
PubMed Reference
Link TM, Park U, Vonakis BM, Raben DM, Soloski MJ, Caterina MJ. TRPV2 has a pivotal role in macrophage particle binding and phagocytosis Nature Immunology (2010) 11, 232-239. PubMed Reference
Landouré G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C Nature Genet. (2010) Feb;42(2):170-4. PubMed Reference
Huang S.M., Lee H., Chung M.K., Park, U., Yu Y.Y., Bradshaw H., Coulombe P.A., Walker J.M., and Caterina M.J. (2008) Skin keratinocyte TRPV3 ion channels modulate pain sensitivity via prostaglandin E2. J. Neurosci. 28, 13727-13737. PubMed Reference
Chung M.K., Guler A.D. and Caterina M.J. (2008) TRPV1 exhibits dynamic ionic selectivity during agonist stimulation Nature Neuroscience 11, 555-564 (Highlighted in Nat Neurosci. 2008 May;11(5):528-9). PubMed Reference
Moussaieff A., Rimmerman N., Bregman T., Straiker A., Felder C.C., Shoham S., Kashman Y., Huang S.M., Lee H., Shohami E., Mackie K., Caterina M.J., Walker J.M., Fride E. and Mechoulam R. (2008) Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain FASEB J 22(8):3024-34. PubMed Reference
Lumpkin, E.A. and Caterina M.J. (2007) Mechanisms of Sensory Transduction in the Skin. Nature 445(7130):858-65. PubMed Reference
Park U, Vastani N, Guan Y, Raja S, Koltzenberg M. and Caterina MJ (2011) TRPV2 knockout mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception J Neurosci. 31(32):11425-36. PubMed Reference
Birder L., Negoita F., Lee H., de Groat W., Kanai A., Barrick S., Meyers S., and Caterina, M.J. (2007) Activation of Urothelial-TRPV4 by 4a-PDD contributes to altered bladder reflexes in the rat J Pharmacol Exp Ther. 323(1):227-35. PubMed Reference
Sidhaye V.K., Guler A.D., Schweitzer K.S., D’Alessio F., Caterina M.J. and King L.S. (2006) Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions. Proc. Natl. Acad. Sci., USA 103(12):4747-52. PubMed Reference
Shimizu I., Iida T., Horiuchi N. and Caterina M.J. (2005) 5-Iodoresiniferatoxin evokes hypothermia in mice and is a partial TRPV1 agonist in vitro J. Pharm. Exp. Ther., 314:1378-85. PubMed Reference
Shimizu I., Iida T., Guan Y., Zhao C., Raja SN, Jarvis M.F., Cockayne D.A., and Caterina M.J. (2005) Enhanced thermal avoidance in mice lacking the ATP receptor P2X3 Pain, 116, 96-108. PubMed Reference
Pogatzki-Zahn E.,, Shimizu I., Caterina, M., and Raja S.N. (2005) Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain. Pain, 115, 296-307. PubMed Reference
Lee, H., Iida, T., Mizuno, A., Suzuki, M., Caterina M.J. Altered thermal preference in mice lacking TRPV4 (2005) J. Neurosci. 25 1304-10. PubMed ReferenceIida, T., Shimizu, I., Nealen, M.L., Campbell, A., and Caterina M.J. Attenuated fever response in mice lacking TRPV1 (2005) Neurosci. Lett. 378, 28-33. PubMed Reference
Chung M.K., Lee H., Mizuno A., Suzuki M., Caterina M.J. 2-aminonethoxydiphenyl borate activates and sensitizes the heat-gated ion channel, TRPV3 (2004) J. Neurosci. 24, 5177-5182. PubMed Reference
Chung M.K., Lee H., Mizuno A., Suzuki M., Caterina M.J. TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes. (2004) J Biol. Chem. 279, 21569-21575. PubMed Reference
Chung, M.K., Lee, H. and Caterina, M.J. Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes (2003) J. Biol. Chem. 278, 32037-32046. PubMed Reference
Nealen, M., Thut, P., Gold, M. and Caterina, M.J. TRPM8 is expressed in a subset of cold-responsive trigeminal neurons from rat. (2003) J. Neurophysiology 90, 515-520. PubMed Reference
Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, Watkins S, Caterina M.J. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. (2002) Nature Neurosci. 5, 856-860. PubMed Reference
Guler, A., Lee, H., Iida, T., Shimizu, I. Tominaga, M., and Caterina, M.J. Heat-evoked activation of the ion channel, TRPV4 (2002) J. Neurosci. 22, 6408-6414. PubMed Reference
Caterina, M.J., Leffler, A., Malmberg, A., Martin,W., Trafton, J., Petersen-Zeitz, K.R., Koltzenberg, M., Basbaum,A. and Julius, D. (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288, 306-313. (cover article) PubMed Reference
Caterina, M.J., Rosen, T.A., Tominaga, M., Brake, A.J., and Julius, D. (1999) A capsaicin receptor homologue with a threshold for noxius heat. Nature, 398, 436-441. PubMed Reference
Caterina, M.J., , Schumacher, M., Tominaga, M.,, Rosen, T.A., Levine, J.D. and Julius, D. (1997) The capsaicin receptor, a heat-activated ion channel in the pain pathway Nature, 389, 816-824. PubMed Reference |