Alternative titles; symbols
HGNC Approved Gene Symbol: TRPV2
Cytogenetic location: 17p11.2 Genomic coordinates (GRCh38) : 17:16,415,571-16,437,003 (from NCBI)
Pain-producing heat is detected by nociceptive sensory neurons that differ in their thermal response thresholds. Capsaicin, the main pungent ingredient in 'hot' chili peppers, is detected by the vanilloid receptor (VR1; 602076). VR1 is a heat-gated ion channel that mediates responses of small-diameter sensory neurons to moderate (43 degrees Celsius) thermal stimuli.
By searching an EST database for sequences related to VR1, followed by probing a myeloid cell line, Caterina et al. (1999) isolated a cDNA encoding TRPV2, which they called VRL1. Sequence analysis predicted that the 764-amino acid VRL1 protein, which is 78% identical to the rat protein, contains 6 transmembrane domains, a putative pore-loop region, a cytoplasmic N terminus with 3 ankyrin-repeat domains, and a C-terminal cytoplasmic tail. Functional analysis showed that cells expressing VRL1 did not respond to capsaicin or low pH, but they did respond to heat over 53 degrees Celsius and to cations. Immunofluorescence microscopy demonstrated expression of Vrl1 in medium- to large-diameter rat dorsal root ganglion neurons and in spinal cord, specifically in Lissauer's tract and the dorsal horn. Northern blot analysis revealed expression of an approximately 2.5-kb Vrl1 transcript in rat sensory ganglia and spinal cord, as well as in lung, spleen, intestine, and multiple brain subregions. Caterina et al. (1999) suggested that nonneuronal tissues expressing VRL1 probably respond to stimuli other than high heat.
The International Radiation Hybrid Mapping Consortium mapped the TRPV2 gene to chromosome 17 (stSG44964).
Muscular dystrophy (DMD; 310200) is a severe degenerative disorder of skeletal muscle characterized by progressive muscle weakness. One subgroup of this disease is caused by a defect in the genes encoding components of the dystrophin-glycoprotein complex (see dystrophin; 300337), resulting in a significant disruption of membrane integrity and/or stability and, consequently, a sustained increase in the cytosolic Ca(2+) concentration. Iwata et al. (2009) demonstrated that muscular dystrophy is ameliorated dystrophin-deficient mdx mice by dominant-negative inhibition of TRPV2. When transgenic (Tg) mice expressing a Trpv2 mutant in muscle were crossed with mdx mice, the cytosolic Ca(2+) concentration increase in muscle fibers was reduced. Histologic, biochemical, and physiologic indices characterizing dystrophic pathology, such as an increased number of central nuclei and fiber size variability/fibrosis/apoptosis, elevated serum creatine kinase levels, and reduced muscle performance, were all ameliorated in the mdx/Tg mice. Iwata et al. (2009) proposed that TRPV2 is a principal Ca(2+)-entry route leading to a sustained [Ca2+]i increase and muscle degeneration.
Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J., Julius, D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398: 436-441, 1999. [PubMed: 10201375] [Full Text: https://doi.org/10.1038/18906]
Iwata, Y., Katanosaka, Y., Arai, Y., Shigekawa, M., Wakabayashi, S. Dominant-negative inhibition of Ca(2+) influx via TRPV2 ameliorates muscular dystrophy in animal models. Hum. Molec. Genet. 18: 824-834, 2009. [PubMed: 19050039] [Full Text: https://doi.org/10.1093/hmg/ddn408]