Subgroup of TRP cation channels named after the vanilloid receptor
Protein family
Transient receptor potential (TRP) ion channel
Homology model of the TRPV1 ion channel tetramer (where the monomers are individually colored cyan, green, blue, and magenta respective) imbedded in a cartoon representation of alipid bilayer.PIP2 signalingligands are represented byspace-filling models (carbon = white, oxygen = red, phosphorus = orange).[1]
TRP channels are a large group ofion channels consisting of six protein families, located mostly on theplasma membrane of numerous human and animal cell types, and in some fungi.[2] TRP channels were initially discovered in thetrp mutant strain of the fruit flyDrosophila[3] that displayed transient elevation of potential in response to light stimuli, and were therefore named "transient receptor potential" channels.[4] The name now refers only to a family of proteins with similar structure and function, not to the mechanism of their activation. Later, TRP channels were found in vertebrates where they are ubiquitously expressed in many cell types and tissues. There are about 28 TRP channels that share some structural similarity to each other.[5] These are grouped into two broad groups: group 1 includesTRPC ( "C" for canonical),TRPV ("V" forvanilloid),TRPM ("M" for melastatin),TRPN andTRPA. In group 2 there areTRPP ("P" for polycystic) andTRPML ("ML" for mucolipin).
Functional TRPV ion channels aretetrameric in structure and are either homo-tetrameric (four identical subunits) or hetero-tetrameric (a total of four subunits selected from two or more types of subunits). The four subunits are symmetrically arranged around the ion conduction pore. Although the extent of heteromerization has been the subject of some debate, the most recent research in this area suggest that all four thermosensitive TRPVs (1-4) can form heteromers with each other. This result is in line with the general observation that TRP coassembly tends to occur between subunits with high sequence similarities. How TRP subunits recognize and interact with each other is still poorly understood.[6][7]
The TRPV channelmonomeric subunit components each contain sixtransmembrane (TM)domains (designated S1–S6) with a pore domain between the fifth (S5) and sixth (S6) segments.[8] TRPV subunits contain three to fiveN-terminalankyrin repeats.[9]
TRPV proteins respond to the taste of garlic (allicin).TRPV1 contributes to heat and inflammation sensations and mediates the pungent odor and pain sensations associated withcapsaicin andpiperine.
Mutations in TRPs have been linked toneurodegenerative disorders, skeletaldysplasia, kidney disorders,[2] and may play an important role in cancer. TRPs may make important therapeutic targets. There is significant clinical significance to TRPV1, TRPV2, and TRPV3's role as thermoreceptors, and TRPV4's role as mechanoreceptors; reduction of chronic pain may be possible by targeting ion channels involved in thermal, chemical, and mechanical sensation to reduce their sensitivity to stimuli.[13] For instance, the use of TRPV1 agonists would potentially inhibitnociception at TRPV1, particularly in pancreatic tissue where TRPV1 is highly expressed.[14] The TRPV1 agonist capsaicin, found in chili peppers, has been indicated to relieve neuropathic pain.[2] TRPV1 antagonists inhibit nociception at TRPV1.
Altered expression of TRP proteins often leads totumorigenesis, clearly seen in TRPM1.[14] Particularly high levels of TRPV6 in prostate cancer have been noted. Such observations could be helpful in following cancer progression and could lead to the development of drugs over activating ion channels, leading toapoptosis andnecrosis. Much research remains to be done as to whether TRP channel mutations lead to cancer progression or whether they are associated mutations.
Four TRPVs (TRPV1, TRPV2, TRPV3, and TRPV4) are expressed inafferentnociceptors, pain sensing neurons, where they act as transducers of thermal and chemical stimuli. Agonists, antagonists, or modulators of these channels may find application for the prevention and treatment of pain.[15] A number of TRPV1 selective blockers such asresiniferatoxin are currently inclinical trials for the treatment of various types of pain.[16]
^Montell C, Rubin GM (April 1989). "Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction".Neuron.2 (4):1313–23.doi:10.1016/0896-6273(89)90069-x.PMID2516726.S2CID8908180.
^Islam MS, ed. (January 2011).Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. Berlin: Springer. p. 700.ISBN978-94-007-0264-6.
^Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels".Pharmacological Reviews.57 (4):427–50.doi:10.1124/pr.57.4.6.PMID16382100.S2CID17936350.
^Szallasi A, Cortright DN, Blum CA, Eid SR (May 2007). "The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept".Nature Reviews. Drug Discovery.6 (5):357–72.doi:10.1038/nrd2280.PMID17464295.S2CID6276214.
"Transient Receptor Potential Channels".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived fromthe original on 2021-10-25. Retrieved2008-12-17.
"TRIP Database".a manually curated database of protein-protein interactions for mammalian TRP channels.
