TRPV — Mediated Wiki

{{Short description|Subgroup of TRP cation channels named after the vanilloid receptor}} {{Pfam_box | Symbol = TRP | Name = Transient receptor potential (TRP) ion channel | image = Trpv1 pip2 bilayer cropped.png | width = | caption = [[Homology modeling|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 a [[lipid bilayer]]. [[Phosphatidylinositol 4,5-bisphosphate|PIP2]] signaling [[ligand (biochemistry)|ligand]]s are represented by [[space-filling model]]s (carbon = white, oxygen = red, phosphorus = orange).<ref name="pmid17548815">{{cite journal | author = Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, Urbina H, Rosenmann E, Gonzalez-Nilo F, Latorre R | title = Dissection of the components for PIP2 activation and thermosensation in TRP channels | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 24 | pages = 10246–51 |date=June 2007 | pmid = 17548815 | pmc = 1891241 | doi = 10.1073/pnas.0703420104 | bibcode = 2007PNAS..10410246B | doi-access = free }}</ref> | Pfam= PF06011 | InterPro= IPR010308 | SMART= | Prosite = | SCOP = | TCDB = | OPM family= | OPM protein= | PDB= }}

'''TRPV''' is a family of [[Transient receptor potential channel|transient receptor potential]] [[ion channel|cation channels]] (TRP channels) in animals. All TRPVs are highly calcium selective.

TRP channels are a large group of [[ion channel]]s consisting of six protein families, located mostly on the [[plasma membrane]] of numerous human and animal cell types, and in some fungi.<ref name="pmid3129667">{{cite journal | vauthors = Winston KR, Lutz W | title = Linear accelerator as a neurosurgical tool for stereotactic radiosurgery | journal = Neurosurgery | volume = 22 | issue = 3 | pages = 454–64 | date = March 1988 | pmid = 3129667 | doi = 10.1097/00006123-198803000-00002 }}</ref> TRP channels were initially discovered in the ''trp'' mutant strain of the fruit fly ''[[Drosophila]]'' <ref>{{cite journal | vauthors = Cosens DJ, Manning A | title = Abnormal electroretinogram from a Drosophila mutant | journal = Nature | volume = 224 | issue = 5216 | pages = 285–7 | date = October 1969 | pmid = 5344615 | doi = 10.1038/224285a0 | bibcode = 1969Natur.224..285C | s2cid = 4200329 }}</ref> that displayed transient elevation of potential in response to light stimuli, and were therefore named "transient receptor potential" channels.<ref>{{cite journal | vauthors = Montell C, Rubin GM | title = Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction | journal = Neuron | volume = 2 | issue = 4 | pages = 1313–23 | date = April 1989 | pmid = 2516726 | doi = 10.1016/0896-6273(89)90069-x | s2cid = 8908180 }}</ref> 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.<ref name = "Islam_2011" >{{cite book | editor = Islam MS | title = Transient Receptor Potential Channels |date=January 2011 | volume = 704 | publisher = Springer | location = Berlin | pages = 700 | series = Advances in Experimental Medicine and Biology | isbn = 978-94-007-0264-6 }}</ref> These are grouped into two broad groups: group 1 includes [[TRPC]] ( "C" for canonical), '''TRPV''' ("V" for [[vanilloid]]), [[TRPM]] ("M" for melastatin), [[TRPN]] and [[TRPA (channel)|TRPA]]. In group 2 there are [[TRPP]] ("P" for polycystic) and [[TRPML]] ("ML" for mucolipin).

== Structure ==

Functional TRPV ion channels are [[tetrameric protein|tetramer]]ic 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.<ref name="vennekens08">{{cite journal | vauthors = Vennekens R, Owsianik G, Nilius B | title = Vanilloid transient receptor potential cation channels: an overview | journal = Current Pharmaceutical Design | volume = 14 | issue = 1 | pages = 18–31 | year = 2008 | pmid = 18220815 | doi = 10.2174/138161208783330763 | url = https://lirias.kuleuven.be/handle/123456789/200319 | url-access = subscription }}</ref><ref name="pmid17325193">{{cite journal |author=Cheng W, Yang F, Takanishi CL, Zheng J |title=Thermosensitive TRPV channel subunits coassemble into heteromeric channels with intermediate conductance and gating properties |journal=[[J. Gen. Physiol.]] |volume=129 |issue=3 |pages=191–207 |date=March 2007 |pmid=17325193 |pmc=2151614 |doi=10.1085/jgp.200709731 }}</ref>

The TRPV channel [[monomer]]ic subunit components each contain six [[transmembrane]] (TM) [[protein domain|domains]] (designated S1–S6) with a pore domain between the fifth (S5) and sixth (S6) segments.<ref name="pmid9535843">{{cite journal | author = Vannier B, Zhu X, Brown D, Birnbaumer L | title = The membrane topology of human transient receptor potential 3 as inferred from glycosylation-scanning mutagenesis and epitope immunocytochemistry | journal = J. Biol. Chem. | volume = 273 | issue = 15 | pages = 8675–9 |date=April 1998 | pmid = 9535843 | doi = 10.1074/jbc.273.15.8675| doi-access = free}}</ref> TRPV subunits contain three to five [[N-terminus|N-terminal]] [[ankyrin repeats]].<ref name="pmid15728426">{{cite journal | author = Montell C | title = The TRP superfamily of cation channels | journal = Sci. STKE | volume = 2005 | issue = 272 | pages = re3 |date=February 2005 | pmid = 15728426 | doi = 10.1126/stke.2722005re3 | s2cid = 7326120 }}</ref>

== Function == TRPV proteins respond to the taste of garlic ([[allicin]]). [[TRPV1]] contributes to heat and inflammation sensations and mediates the [[pungency]] and pain sensation associated with [[capsaicin]] and [[piperine]].

== Family members ==

The table below summarizes the functions and properties of the individual TRPV channel family members:<ref name="pmid16382100">{{cite journal | vauthors = Clapham DE, Julius D, Montell C, Schultz G | title = International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 427–50 | date = December 2005 | pmid = 16382100 | doi = 10.1124/pr.57.4.6 | s2cid = 17936350 }}</ref><ref name="annrevbc07">{{cite journal | vauthors = Venkatachalam K, Montell C | title = TRP channels | journal = Annual Review of Biochemistry | volume = 76 | issue = 1 | pages = 387–417 | year = 2007 | pmid = 17579562 | doi = 10.1146/annurev.biochem.75.103004.142819 | pmc = 4196875 }}</ref> {| class="wikitable" border="1" style="text-align:center" |- ! width="40"|group ! width="40"|channel ! width="120"|function ! width="100"|tissue distribution ! width="60"|Ca2+/Na+ selectivity ! width="100"|heteromeric associated subunits ! width="100"|other associated proteins |- | rowspan=4|1 | [[TRPV1]] | vanilloid (capsaicin) receptor and noxious [[thermoreceptor|thermosensor]] (43 °C) | [[Central nervous system|CNS]] and [[Peripheral nervous system|PNS]] | 9:1 | TRPV2, TRPV3 | [[calmodulin]], [[Phosphoinositide 3-kinase|PI3 kinase]] |- | [[TRPV2]] | [[osmoreceptor|osmo]]- and noxious heat thermosensor (52 °C) | CNS, spleen and lung | 3:1 | TRPV1 | |- | [[TRPV3]] | warmth sensor channel (33-39 °C) | Skin, CNS and PNS | 12:1 | TRPV1 | |- | [[TRPV4]] | osmo- and warmth sensor channel (27-34 °C) | CNS and internal organs; human sperm<ref>{{cite journal | vauthors = Mundt N, Spehr M, Lishko PV | title = TRPV4 is the temperature-sensitive ion channel of human sperm | journal = eLife | volume = 7 | date = July 2018 | pmid = 29963982 | pmc = 6051745 | doi = 10.7554/elife.35853 | doi-access = free }}</ref> | 6:1 | | [[AQP5|aquaporin 5]], calmodulin, [[PACSIN3|pacsin 3]] |- | rowspan=2|2 | [[TRPV5]] | calcium-selective TRP channel | intestine, kidney, placenta | 100:1 | TRPV6 | [[ANXA2|annexin II]] / [[S100A10]], calmodulin |- | [[TRPV6]] | calcium-selective TRP channel | kidney, intestine | 130:1 | TRPV5 | annexin II / S100A10, calmodulin |}

== Clinical significance ==

Mutations in TRPs have been linked to [[neurodegeneration|neurodegenerative]] disorders, skeletal [[dysplasia]], kidney disorders,<ref name="pmid3129667"/> 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.<ref>{{cite journal | vauthors = Levine JD, Alessandri-Haber N | title = TRP channels: targets for the relief of pain | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1772 | issue = 8 | pages = 989–1003 | date = August 2007 | pmid = 17321113 | doi = 10.1016/j.bbadis.2007.01.008 | s2cid = 11450214 | url = https://hal.archives-ouvertes.fr/hal-00562760/file/PEER_stage2_10.1016%252Fj.bbadis.2007.01.008.pdf }}</ref> For instance, the use of TRPV1 agonists would potentially inhibit [[nociception]] at TRPV1, particularly in pancreatic tissue where TRPV1 is highly expressed.<ref name="pmid17616360">{{cite journal | vauthors = Prevarskaya N, Zhang L, Barritt G | title = TRP channels in cancer | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1772 | issue = 8 | pages = 937–46 | date = August 2007 | pmid = 17616360 | doi = 10.1016/j.bbadis.2007.05.006 | url = https://hal.archives-ouvertes.fr/hal-00562788/file/PEER_stage2_10.1016%252Fj.bbadis.2007.05.006.pdf }}</ref> The TRPV1 agonist capsaicin, found in chili peppers, has been indicated to relieve neuropathic pain.<ref name="pmid3129667"/> TRPV1 antagonists inhibit nociception at TRPV1.

==Role in cancer== Altered expression of TRP proteins often leads to [[tumorigenesis]], clearly seen in TRPM1.<ref name="pmid17616360"/> 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 to [[apoptosis]] and [[necrosis]]. Much research remains to be done as to whether TRP channel mutations lead to cancer progression or whether they are associated mutations.

== As drug targets == Four TRPVs (TRPV1, TRPV2, TRPV3, and TRPV4) are expressed in [[afferent nerve|afferent]] [[nociceptor]]s, 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.<ref name="pmid17321113">{{cite journal | author = Levine JD, Alessandri-Haber N | title = TRP channels: targets for the relief of pain | journal = Biochim. Biophys. Acta | volume = 1772 | issue = 8 | pages = 989–1003 |date=August 2007 | pmid = 17321113 | doi = 10.1016/j.bbadis.2007.01.008 | s2cid = 11450214 | url = https://hal.archives-ouvertes.fr/hal-00562760/file/PEER_stage2_10.1016%252Fj.bbadis.2007.01.008.pdf}}</ref> A number of TRPV1 selective [[agonist]]s and [[Receptor antagonist|antagonist]]s such as [[resiniferatoxin]] were in [[clinical trial]]s for the treatment of various types of pain.<ref name="pmid17464295">{{cite journal | vauthors = Szallasi A, Cortright DN, Blum CA, Eid SR | title = The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept | journal = Nature Reviews. Drug Discovery | volume = 6 | issue = 5 | pages = 357–72 | date = May 2007 | pmid = 17464295 | doi = 10.1038/nrd2280 | s2cid = 6276214 }}</ref>

== See also == * [[Discovery and development of TRPV1 antagonists]] * [[TRPA1]]

== References == {{Reflist|32em}}

== External links == * {{MeshName|Transient+Receptor+Potential+Channels}} * {{cite web | url = http://www.iuphar-db.org/IC/FamilyMenuForward?familyId=12 | title = Transient Receptor Potential Channels | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2008-12-17 | archive-date = 2021-10-25 | archive-url = https://web.archive.org/web/20211025112234/https://www.iuphar-db.org/IC/FamilyMenuForward?familyId=12 | url-status = dead }} * {{cite web | url = http://www.trpchannel.org | title = TRIP Database | work = a manually curated database of protein-protein interactions for mammalian TRP channels}}

[[Category:Membrane proteins]] [[Category:Ion channels]]