1 Signalling Programme, Babraham Institute, Cambridge, CB2 4AT, UK
2 Bioinoformatics Department, Babraham Institute, Cambridge, CB2 4AT, UK
* Author for correspondence (e-mail: raghu.padinjat{at}bbsrc.ac.uk)
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Estimates of the numbers of TRP channels in fully sequenced genomes vary depending on the inclusion of outlying but related family numbers. More than 100 TRP sequences are present in current non-redundant database sets, including members from Saccharomyces cerevisiae, Dictyostelium discoideum, Caenorhabditis elegans, Drosophila and mammals. A phylogenetic tree representing the relatedness of these sequences is presented in the accompanying poster. Recently, a unified nomenclature for these channels has been proposed and accepted by the HUGO gene Nomenclature Committee for all future publications on mammalian TRP channels (Montell et al., 2002). This system defines three broad families of TRP channels: TRPC, TRPV and TRPM. The TRPC family (C is for canonical) is composed of proteins most closely related to the original Drosophila TRP channel. The TRPV family is named after the original name of the founding member of this family the vanilloid receptor VR-1 and TRPM is named after the founding member of its family melastatin. Additional but more distantly related families of TRP channels, such as the polycystins, mucolipins and ANKTM have been identified (Clapham, 2003
). The estimated numbers of TRP genes of different families can be found in the table on the poster.
![]() |
Structure of TRP channels |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
By analogy with the structure of more distantly related channels, such as the K+ channel KcsA (Doyle et al., 1998) and the cyclic-nucleotide-gated channel (Kaupp and Seifert, 2002
), it is expected that TRP channels exist as oligomers. Although evidence has been presented for hetero-oligomers in overexpression systems for both TRPC (Hofmann et al., 2002
; Strubing et al., 2001
; Strubing et al., 2003
; Xu et al., 1997
) and TRPV channels (Kedei et al., 2001
) the exact composition of the oligomers in vivo, and the functional consequences of oligomerization, if any, remain controversial (Reuss et al., 1997
; Xu et al., 1997
).
![]() |
Physiological functions of TRP channels |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Sensory transduction
Drosophila TRP is the major component of the light-activated conductance in Drosophila photoreceptors (Hardie and Minke, 1992). Since then a number of other TRP channels from all three subfamilies have been implicated in sensory transduction processes in vivo and in heterologous systems. It is clear from these studies that TRP channels respond to a wide range of sensory stimuli in a number of different organisms. A summary of these is given in the poster.
Development
TRP channels have been shown to function or have been implicated in a number of developmental process. The cell divisions required for gonad development in C. elegans require GON-2, a TRPM channel (West et al., 2001). Fertilization is thought to be mediated by a series of sperm-egg interactions. TRPC channels have been shown to play a role in this process both in mouse (TRPC2) (West et al., 2001
) and in C. elegans (TRP-3) (Xu and Sternberg, 2003
). Recent studies have suggested that Ca2+ signalling mediated by polycystin 2, a distant member of the TRP superfamily, might be one of the primary events in the establishment of left-right asymmetry in early vertebrate embryogenesis (McGrath et al., 2003
). In cell culture experiments, TRPV2 channels are known to undergo translocation to the plasma membrane from an intracellular pool, following stimulation with insulin-like growth factor 1 (Kanzaki et al., 1999
), which suggests a role for Ca2+ influx through TRP channels during development.
![]() |
TRP channels and human disease |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Acharya, J. K., Jalink, K., Hardy, R. W., Hartenstein, V. and Zuker, C. S. (1997). InsP3 receptor is essential for growth and differentiation but not for vision in Drosophila. Neuron 18, 881-887.[Medline]
Clapham, D. E. (2003). TRP channels as cellular sensors. Nature 426, 517-524.[CrossRef][Medline]
Cosens, D. J. and Manning, A. (1969). Abnormal electroretinogram from a Drosophila mutant. Nature 224, 285-287.[Medline]
den Dekker, E., Hoenderop, J. G., Nilius, B. and Bindels, R. J. (2003). The epithelial calcium channels, TRPV5 & TRPV6: from identification towards regulation. Cell Calcium 33, 497-507.[CrossRef][Medline]
Doyle, D. A., Morais Cabral, J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T. and MacKinnon, R. (1998). The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69-77.
Duncan, L. M., Deeds, J., Cronin, F. E., Donovan, M., Sober, A. J., Kauffman, M. and McCarthy, J. J. (2001). Melastatin expression and prognosis in cutaneous malignant melanoma. J. Clin. Oncol. 19, 568-576.
Hardie, R. C. (2003). Regulation of TRP channels via lipid second messengers. Annu. Rev. Physiol. 65, 735-759.[CrossRef][Medline]
Hardie, R. C. and Minke, B. (1992). The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron 8, 643-651.[Medline]
Hofmann, T., Schaefer, M., Schultz, G. and Gudermann, T. (2002). Subunit composition of mammalian transient receptor potential channels in living cells. Proc. Natl. Acad. Sci. USA 99, 7461-7466.
Kanzaki, M., Zhang, Y. Q., Mashima, H., Li, L., Shibata, H. and Kojima, I. (1999). Translocation of a calcium-permeable cation channel induced by insulin-like growth factor-I. Nat. Cell Biol. 1, 165-170.[CrossRef][Medline]
Kaupp, U. B. and Seifert, R. (2002). Cyclic nucleotide-gated ion channels. Physiol. Rev. 82, 769-824.
Kedei, N., Szabo, T., Lile, J. D., Treanor, J. J., Olah, Z., Iadarola, M. J. and Blumberg, P. M. (2001). Analysis of the native quaternary structure of vanilloid receptor 1. J. Biol. Chem. 276, 28613-28619.
McGrath, J., Somlo, S., Makova, S., Tian, X. and Brueckner, M. (2003). Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114, 61-73.[Medline]
Mochizuki, T., Wu, G., Hayashi, T., Xenophontos, S. L., Veldhuisen, B., Saris, J. J., Reynolds, D. M., Cai, Y., Gabow, P. A., Pierides, A. et al. (1996). PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272, 1339-1342.[Abstract]
Monteilh-Zoller, M. K., Hermosura, M. C., Nadler, M. J. S., Scharenberg, A. M., Penner, R. and Fleig, A. (2002). TRPM7 Provides an Ion Channel Mechanism for Cellular Entry of Trace Metal Ions. J. Gen. Physiol. 121, 49-60.[CrossRef]
Montell, C. (2001). Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci. STKE 90, RE1.
Montell, C. and Rubin, G. M. (1989). Molecular characterization of the Drosophila trp locus a putative integral membrane-protein required for phototransduction. Neuron 2, 1313-1323.[Medline]
Montell, C., Birnbaumer, L., Flockerzi, V., Bindels, R. J., Bruford, E. A., Caterina, M. J., Clapham, D. E., Harteneck, C., Heller, S., Julius, D. et al. (2002). A unified nomenclature for the superfamily of TRP cation channels. Mol. Cell 9, 229-231.[Medline]
Putney, J. W., Jr and McKay, R. R. (1999). Capacitative calcium entry channels. Bioessays 21, 38-46.[CrossRef][Medline]
Raghu, P., Colley, N. J., Webel, R., James, T., Hasan, G., Danin, M., Selinger, Z. and Hardie, R. C. (2000). Normal phototransduction in Drosophila photoreceptors lacking an InsP(3) receptor gene. Mol. Cell Neurosci. 15, 429-445.[CrossRef][Medline]
Reuss, H., Mojet, M. H., Chyb, S. and Hardie, R. C. (1997). In vivo analysis of the Drosophila light-sensitive channels, TRP and TRPL. Neuron 19, 1249-1259.[Medline]
Strubing, C., Krapivinsky, G., Krapivinsky, L. and Clapham, D. E. (2001). TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29, 645-655.[Medline]
Strubing, C., Krapivinsky, G., Krapivinsky, L. and Clapham, D. E. (2003). Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J. Biol. Chem. 278, 39014-39019.
Sun, M., Goldin, E., Stahl, S., Falardeau, J. L., Kennedy, J. C., Acierno, J. S., Jr, Bove, C., Kaneski, C. R., Nagle, J., Bromley, M. C. et al. (2000). Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel. Hum. Mol. Genet. 9, 2471-2478.
Tsavaler, L., Shapero, M. H., Morkowski, S. and Laus, R. (2001). Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 61, 3760-3769.
West, R. J., Sun, A. Y., Church, D. L. and Lambie, E. J. (2001). The C. elegans gon-2 gene encodes a putative TRP cation channel protein required for mitotic cell cycle progression. Gene 266, 103-110.[CrossRef][Medline]
Xu, X. Z. and Sternberg, P. W. (2003). A C. elegans sperm TRP protein required for sperm-egg interactions during fertilization. Cell 114, 285-297.[Medline]
Xu, X. Z. S., Li, H. S., Guggino, W. B. and Montell, C. (1997). Coassembly of TRP and TRPL produces a distinct store-operated conductance. Cell 89, 1155-1164.[Medline]
Zitt, C., Halaszovich, C. R. and Luckhoff, A. (2002). The TRP family of cation channels: probing and advancing the concepts on receptor-activated calcium entry. Prog. Neurobiol. 66, 243-264.[CrossRef][Medline]