TRPV3 is a temperature-sensitive vanilloid receptor-like protein

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments—such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons—suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 °C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.

[1]  I. Nagy,et al.  Similarities and Differences between the Responses of Rat Sensory Neurons to Noxious Heat and Capsaicin , 1999, Journal of Neuroscience.

[2]  J. Hoenderop,et al.  Gene structure and chromosomal mapping of human epithelial calcium channel. , 2000, Biochemical and biophysical research communications.

[3]  A I Basbaum,et al.  Impaired nociception and pain sensation in mice lacking the capsaicin receptor. , 2000, Science.

[4]  J Schultz,et al.  SMART, a simple modular architecture research tool: identification of signaling domains. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C. Heid,et al.  A novel method for real time quantitative RT-PCR. , 1996, Genome research.

[6]  P. Séguéla,et al.  Mammalian ASIC2a and ASIC3 Subunits Co-assemble into Heteromeric Proton-gated Channels Sensitive to Gd3+ * , 2000, The Journal of Biological Chemistry.

[7]  S. Weremowicz,et al.  Human calcium transport protein CaT1. , 2000, Biochemical and biophysical research communications.

[8]  S. Topp,et al.  Cloning and functional expression of a human orthologue of rat vanilloid receptor-1 , 2000, Pain.

[9]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[10]  A. D. den Hollander,et al.  Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial Ca2+ channel (ECAC1). , 2000, Genomics.

[11]  S. Karlin,et al.  Prediction of complete gene structures in human genomic DNA. , 1997, Journal of molecular biology.

[12]  C. Southan,et al.  Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. , 2000, European journal of biochemistry.

[13]  E. Green,et al.  The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion. , 2000, Genome research.

[14]  T. Carlstedt,et al.  Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states , 2000, Pain.

[15]  E. Brown,et al.  Structural conservation of the genes encoding CaT1, CaT2, and related cation channels. , 2001, Genomics.

[16]  S. Bingham,et al.  Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia , 2000, Nature.

[17]  A. Hudspeth,et al.  Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor , 2000, Cell.

[18]  Craig Montell,et al.  A unified nomenclature for the superfamily of TRP cation channels. , 2002, Molecular cell.

[19]  R. Durbin,et al.  Using GeneWise in the Drosophila annotation experiment. , 2000, Genome research.

[20]  Kay Hofmann,et al.  Tmbase-A database of membrane spanning protein segments , 1993 .

[21]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[22]  P. Emson,et al.  Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study. , 2001, Biochimica et biophysica acta.

[23]  J. Chambers,et al.  The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1) , 2000, British journal of pharmacology.

[24]  John Dempster,et al.  Computer analysis of electrophysiological signals , 1993 .

[25]  A. Randall,et al.  The diversity in the vanilloid (TRPV) receptor family of ion channels. , 2002, Trends in pharmacological sciences.

[26]  P Facer,et al.  Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. , 2001, Physiological genomics.

[27]  G. Burnstock,et al.  Coexpression of P2X(3) and P2X(2) receptor subunits in varying amounts generates heterogeneous populations of P2X receptors that evoke a spectrum of agonist responses comparable to that seen in sensory neurons. , 2001, The Journal of pharmacology and experimental therapeutics.

[28]  D. Julius,et al.  A capsaicin-receptor homologue with a high threshold for noxious heat , 1999, Nature.