Editing Transient receptor potential channel

{{Short description|Class of transport proteins}}
{{Infobox protein family
 | Symbol = TRP 
 | Name = Transient receptor potential (TRP) ion channel 
 | image = 
 | width = 
 | caption = 
 | Pfam= PF06011
 | InterPro= IPR013555
 | SMART= 
 | Prosite =          
 | SCOP =     
 | TCDB = 
 | OPM family= 8
 | OPM protein= 3j5p
 | PDB= 
 | Membranome superfamily = 605
}} 
'''Transient receptor potential channels''' ('''TRP channels''') are a group of [[ion channel]]s located mostly on the [[plasma membrane]] of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes [[TRPC]] ( "C" for canonical), [[TRPV]] ("V" for [[vanilloid]]), [[TRPVL]] ("VL" for vanilloid-like), [[TRPM]] ("M" for melastatin), [[TRPS]] ("S" for soromelastatin), [[TRPN]] ("N" for mechanoreceptor potential C), and [[TRPA (channel)|TRPA]] ("A" for ankyrin). Group 2 consists of [[TRPP]] ("P" for polycystic) and [[TRPML]] ("ML" for mucolipin).<ref name = "Islam_2011">{{cite book | veditors = 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><ref name="TRP_review" /> Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals.<ref name="TRP_review" /><ref>{{cite journal | vauthors = Arias-Darraz L, Cabezas D, Colenso CK, Alegría-Arcos M, Bravo-Moraga F, Varas-Concha I, Almonacid DE, Madrid R, Brauchi S | display-authors = 6 | title = A transient receptor potential ion channel in Chlamydomonas shares key features with sensory transduction-associated TRP channels in mammals | journal = The Plant Cell | volume = 27 | issue = 1 | pages = 177–88 | date = January 2015 | pmid = 25595824 | pmc = 4330573 | doi = 10.1105/tpc.114.131862 | doi-access = free | bibcode = 2015PlanC..27..177A }}</ref><ref>{{cite journal | vauthors = Lindström JB, Pierce NT, Latz MI | title = Role of TRP Channels in Dinoflagellate Mechanotransduction | journal = The Biological Bulletin | volume = 233 | issue = 2 | pages = 151–167 | date = October 2017 | pmid = 29373067 | doi = 10.1086/695421 | s2cid = 3388001 }}</ref> Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of taste, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold.<ref name="pmid25053448">
{{cite journal | vauthors = Vriens J, Nilius B, Voets T | title = Peripheral thermosensation in mammals | journal = Nature Reviews. Neuroscience | volume = 15 | issue = 9 | pages = 573–89 | date = September 2014 | pmid = 25053448 | doi = 10.1038/nrn3784 | s2cid = 27149948 | doi-access = free }}</ref> Some TRP channels are activated by molecules found in spices like garlic ([[allicin]]), chili pepper ([[capsaicin]]), wasabi ([[allyl isothiocyanate]]); others are activated by [[menthol]], [[camphor]], peppermint, and cooling agents; yet others are activated by molecules found in [[cannabis]] (i.e., [[THC]], [[cannabidiol|CBD]] and [[Cannabinol|CBN]]) or [[Stevia rebaudiana|stevia]]. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of [[lipid-gated ion channels]].<ref>{{cite journal | vauthors = Robinson CV, Rohacs T, Hansen SB | title = Tools for Understanding Nanoscale Lipid Regulation of Ion Channels | journal = Trends in Biochemical Sciences | volume = 44 | issue = 9 | pages = 795–806 | date = September 2019 | pmid = 31060927 | pmc = 6729126 | doi = 10.1016/j.tibs.2019.04.001 }}</ref><ref>{{cite journal | vauthors = Hansen SB | title = Lipid agonism: The PIP2 paradigm of ligand-gated ion channels | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1851 | issue = 5 | pages = 620–8 | date = May 2015 | pmid = 25633344 | pmc = 4540326 | doi = 10.1016/j.bbalip.2015.01.011 }}</ref>

These [[ion channel]]s have a relatively non-selective permeability to [[cation]]s, including [[sodium]], [[calcium]] and [[magnesium]].

TRP channels were initially discovered in the so-called "transient receptor potential" mutant (''trp''-mutant) strain of the fruit fly ''[[Drosophila]]'', hence their name (see [[Transient receptor potential channel#History of Drosophila TRP channels|History of ''Drosophila'' TRP channels]] below). Later, TRP channels were found in vertebrates where they are ubiquitously expressed in many cell types and tissues. TRP channels are tetrameric, with each protomer composed of 6 [[Alpha helix#Membrane spanning|membrane-spanning helices]] with intracellular N- and [[C terminus|C-termini]]. Mammalian TRP channels are activated and regulated by a wide variety of stimuli and are expressed throughout the body.

== Families ==
[[File:TRP Channel Phylogeny.svg|right|thumb|500px|TRP channel groups and families.]]

In the animal TRP superfamily there are currently 9 proposed families split into two groups, each family containing a number of subfamilies.<ref name="TRP_review" /> Group one consists of TRPC, TRPV, TRPVL, TRPA, TRPM, TRPS, and TRPN, while group two contains TRPP and TRPML. There is an additional family labeled TRPY that is not always included in either of these groups. All of these sub-families are similar in that they are molecular sensing, non-selective cation channels that have six transmembrane segments, however, each sub-family is unique and shares little structural homology with one another. This uniqueness gives rise to the various sensory perception and regulation functions that TRP channels have throughout the body. Group one and group two vary in that both TRPP and TRPML of group two have a much longer extracellular loop between the S1 and S2 transmembrane segments. Another differentiating characteristic is that all the group one sub-families either contain an N-terminal intracellular ankyrin repeat sequence, a C-terminal TRP domain sequence, or both—whereas both group two sub-families have neither.<ref name="Kadowaki_evodyn">{{cite journal | vauthors = Kadowaki T | title = Evolutionary dynamics of metazoan TRP channels | journal = Pflügers Archiv | volume = 467 | issue = 10 | pages = 2043–53 | date = October 2015 | pmid = 25823501 | doi = 10.1007/s00424-015-1705-5 | s2cid = 9190224 }}</ref> Below are members of the sub-families and a brief description of each:

===TRPA===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref>{{cite journal | vauthors = Kang K, Pulver SR, Panzano VC, Chang EC, Griffith LC, Theobald DL, Garrity PA | title = Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception | journal = Nature | volume = 464 | issue = 7288 | pages = 597–600 | date = March 2010 | pmid = 20237474 | pmc = 2845738 | doi = 10.1038/nature08848 | bibcode = 2010Natur.464..597K }}</ref><ref name="Drosophila menthol sensitivity">{{cite journal | vauthors = Himmel NJ, Letcher JM, Sakurai A, Gray TR, Benson MN, Cox DN | title = ''Drosophila'' menthol sensitivity and the Precambrian origins of transient receptor potential-dependent chemosensation | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 374 | issue = 1785 | pages = 20190369 | date = November 2019 | pmid = 31544603 | pmc = 6790378 | doi = 10.1098/rstb.2019.0369 }}</ref><ref name="Peng">{{cite journal | vauthors = Peng G, Shi X, Kadowaki T | title = Evolution of TRP channels inferred by their classification in diverse animal species | journal = Molecular Phylogenetics and Evolution | volume = 84 | pages = 145–57 | date = March 2015 | pmid = 24981559 | doi = 10.1016/j.ympev.2014.06.016 | bibcode = 2015MolPE..84..145P }}</ref>
|-
|rowspan="7" |TRPA
|[[TRPA1]]
|[[Vertebrates]], [[arthropods]], and [[molluscs]]
|-
|TRPA-like
|[[Choanoflagellates]], [[cnidarians]], [[nematodes]], arthropods (only crustaceans and myriapods), molluscs, and [[echinoderms]]
|-
|TRPA5
|rowspan="4" |Arthropods (only crustaceans and insects)
|-
|painless
|-
|pyrexia
|-
|waterwitch
|-
|HsTRPA
|Specific to [[hymenopteran]] insects
|}
TRPA, A for "ankyrin", is named for the large amount of ankyrin repeats found near the N-terminus.<ref name=":4">{{cite journal | vauthors = Moran MM, McAlexander MA, Bíró T, Szallasi A | title = Transient receptor potential channels as therapeutic targets | journal = Nature Reviews. Drug Discovery | volume = 10 | issue = 8 | pages = 601–20 | date = August 2011 | pmid = 21804597 | doi = 10.1038/nrd3456 | s2cid = 8809131 }}</ref> TRPA is primarily found in afferent nociceptive nerve fibers and is associated with the amplification of pain signaling as well as cold pain hypersensitivity. These channels have been shown to be both mechanical receptors for pain and chemosensors activated by various chemical species, including isothiocyanates (pungent chemicals in substances such as mustard oil and wasabi), cannabinoids, general and local analgesics, and cinnamaldehyde.<ref name=":3" />

While TRPA1 is expressed in a wide variety of animals, a variety of other TRPA channels exist outside of vertebrates.  TRPA5, painless, pyrexia, and waterwitch are distinct phylogenetic branches within the TRPA clade, and are only evidenced to be expressed in crustaceans and insects,<ref name="Kadowaki_evodyn"/> while HsTRPA arose as a Hymenoptera-specific duplication of waterwitch.<ref>{{cite journal | vauthors = Kohno K, Sokabe T, Tominaga M, Kadowaki T | title = Honey bee thermal/chemical sensor, AmHsTRPA, reveals neofunctionalization and loss of transient receptor potential channel genes | journal = The Journal of Neuroscience | volume = 30 | issue = 37 | pages = 12219–29 | date = September 2010 | pmid = 20844118 | pmc = 6633439 | doi = 10.1523/JNEUROSCI.2001-10.2010 }}</ref> Like TRPA1 and other TRP channels, these function as ion channels in a number of sensory systems. TRPA- or TRPA1-like channels also exists in a variety of species as a phylogenetically distinct clade, but these are less well understood.<ref name="Drosophila menthol sensitivity"/>

===TRPC===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref name="Peng" /><ref>{{cite journal | vauthors = French AS, Meisner S, Liu H, Weckström M, Torkkeli PH | title = Transcriptome analysis and RNA interference of cockroach phototransduction indicate three opsins and suggest a major role for TRPL channels | journal = Frontiers in Physiology | volume = 6 | pages = 207 | date = 2015 | pmid = 26257659 | pmc = 4513288 | doi = 10.3389/fphys.2015.00207 | doi-access = free }}</ref><ref name="Himmel2">{{cite journal |vauthors=Himmel NJ, Gray TR, Cox DN |date=July 2020 |title=Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS) |journal=Molecular Biology and Evolution |volume=37 |issue=7 |pages=2034–2044 |doi=10.1093/molbev/msaa065 |pmc=7306681 |pmid=32159767 |doi-access=free}}</ref>
|-
|rowspan="11" |TRPC
|[[TRPC1]]
|rowspan="7" |Vertebrates
|-
|[[TRPC2]]
|-
|[[TRPC3]]
|-
|[[TRPC4]]
|-
|[[TRPC5]]
|-
|[[TRPC6]]
|-
|[[TRPC7]]
|-
|TRP
|rowspan="3" |Arthropods
|-
|TRPgamma
|-
|TRPL
|-
|Unknown
|Choanoflagellates, cnidarians, [[xenacoelomorpha|xenacoelomorphs]], [[lophotrochozoa]]ns, and nematodes
|}
TRPC, C for "canonical", is named for being the most closely related to ''Drosophila'' TRP, the namesake of TRP channels.  The phylogeny of TRPC channels has not been resolved in detail, but they are present across animal taxa.  There are actually only six TRPC channels expressed in humans because TRPC2 is found to be expressed solely in mice and is considered a [[Pseudogene|pseudo-gene]] in humans; this is partly due to the role of TRPC2 in detecting pheromones, which mice have an increased ability compared to humans. Mutations in TRPC channels have been associated with respiratory diseases along with [[focal segmental glomerulosclerosis]] in the kidneys.<ref name=":3">{{Cite book|title=TRP channels as therapeutic targets : from basic science to clinical use|others=Szallasi, Arpad, 1958-, McAlexander, M. Allen|isbn=9780124200791|location=Amsterdam [Netherlands]|oclc=912315205| vauthors = Szallasi A |date=2015-04-09}}</ref> All TRPC channels are activated either by [[phospholipase C]] (PLC) or [[Diglyceride|diacyglycerol]] (DAG).

===TRPML===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref name="Peng" /><ref name="Garcia TRML">{{cite book | vauthors = García-Añoveros J, Wiwatpanit T | chapter = TRPML2 and Mucolipin Evolution | title = Mammalian Transient Receptor Potential (TRP) Cation Channels | series = Handbook of Experimental Pharmacology | volume = 222 | pages = 647–58 | date = 2014 | pmid = 24756724 | doi = 10.1007/978-3-642-54215-2_25 | isbn = 978-3-642-54214-5 }}</ref>
|-
| rowspan="4" |TRPML
|Unknown
| Cnidarians, basal vertebrates, [[tunicates]], [[cephalochordates]], [[hemichordates]], echinoderms, arthropods, and nematodes
|-
|[[MCOLN1|TRPML1]]
| rowspan="3" |Specific to jawed vertebrates
|-
|[[MCOLN2|TRPML2]]
|-
|[[MCOLN3|TRPML3]]
|}
TRPML, ML for "mucolipin", gets its name from the neurodevelopmental disorder [[Mucolipidosis type IV|mucolipidosis IV]]. Mucolipidosis IV was first discovered in 1974 by E.R. Berman who noticed abnormalities in the eyes of an infant.<ref>{{cite journal | vauthors = Berman ER, Livni N, Shapira E, Merin S, Levij IS | title = Congenital corneal clouding with abnormal systemic storage bodies: a new variant of mucolipidosis | journal = The Journal of Pediatrics | volume = 84 | issue = 4 | pages = 519–26 | date = April 1974 | pmid = 4365943 | doi = 10.1016/s0022-3476(74)80671-2 }}</ref> These abnormalities soon became associated with mutations to the MCOLN1 gene which encodes for the TRPML1 ion channel. TRPML is still not highly characterized.  The three known vertebrate copies are restricted to jawed vertebrates, with some exceptions (e.g. ''[[Xenopus tropicalis]]'').<ref name="Garcia TRML" />

===TRPM===
{| class="wikitable"
!Family !!Sub-Family !! Known Taxa
|-
|rowspan="2" |TRPM
|Alpha/α (inc. TRPM1, 3, 6, and 7)
| rowspan="2"|All [[choanoflagellate]]s and [[eumetazoa]] (except [[tardigrades]])
|-
|Beta/β (inc. TRPM2, 4, 5, and 8)
|}
TRPM, M for "melastatin", was found during a comparative genetic analysis between benign [[Nevus|nevi]] and malignant nevi (melanoma).<ref name=":4" /> Mutations within TRPM channels have been associated with hypomagnesemia with secondary hypocalcemia. TRPM channels have also become known for their cold-sensing mechanisms, such is the case with TRPM8.<ref name=":3" />  Comparative studies have shown that the functional domains and critical amino acids of TRPM channels are highly conserved across species.<ref>{{cite journal |vauthors=Mederos y Schnitzler M, Wäring J, Gudermann T, Chubanov V |date=May 2008 |title=Evolutionary determinants of divergent calcium selectivity of TRPM channels |journal=FASEB Journal |volume=22 |issue=5 |pages=1540–51 |doi=10.1096/fj.07-9694com |doi-access=free |pmid=18073331 |s2cid=25474094}}</ref><ref name="Drosophila menthol sensitivity" /><ref>{{cite journal |vauthors=Iordanov I, Tóth B, Szollosi A, Csanády L |date=April 2019 |title=Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates |journal=eLife |volume=8 |doi=10.7554/eLife.44556 |pmc=6461439 |pmid=30938679 |doi-access=free }}</ref>

[[Phylogenetics]] has shown that TRPM channels are split into two major clades, αTRPM and βTRPM.<ref name="Drosophila menthol sensitivity" /><ref name="Himmel2" /> αTRPMs include vertebrate TRPM1, TRPM3, and the "chanzymes" TRPM6 and TRPM7, as well as the only insect TRPM channel, among others. βTRPMs include, but are not limited to, vertebrate TRPM2, TRPM4, TRPM5, and TRPM8 (the cold and menthol sensor).  Two additional major clades have been described: TRPMc, which is present only in a variety of arthropods,<ref name="Himmel2" /> and a basal clade,<ref name="Peng" /><ref name="Drosophila menthol sensitivity" /> which has since been proposed to be a distinct and separate TRP channel family (TRPS).<ref name="Himmel2" />

===TRPN===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref name="Schuler">{{cite journal | vauthors = Schüler A, Schmitz G, Reft A, Özbek S, Thurm U, Bornberg-Bauer E | title = The Rise and Fall of TRP-N, an Ancient Family of Mechanogated Ion Channels, in Metazoa | journal = Genome Biology and Evolution | volume = 7 | issue = 6 | pages = 1713–27 | date = June 2015 | pmid = 26100409 | pmc = 4494053 | doi = 10.1093/gbe/evv091 }}</ref><ref name="Peng" />
|-
|TRPN
|TRPN/nompC
|Placozoans, cnidarians, nematodes, arthropods, molluscs, [[annelids]], and vertebrates (excluding amniotes)
|}
TRPN was originally described in ''Drosophila melanogaster'' and ''Caenorhabditis elegans'' as nompC, a mechanically gated ion channel.<ref>{{cite journal | vauthors = Walker RG, Willingham AT, Zuker CS | title = A Drosophila mechanosensory transduction channel | journal = Science | volume = 287 | issue = 5461 | pages = 2229–34 | date = March 2000 | pmid = 10744543 | doi = 10.1126/science.287.5461.2229 | bibcode = 2000Sci...287.2229W }}</ref><ref name="Schuler" /> Only a single TRPN, N for "no mechanoreceptor potential C," or "nompC", is known to be broadly expressed in animals (although some Cnidarians have more), and is notably only a [[pseudogene]] in [[amniote]] vertebrates.<ref name="Schuler" /><ref name="Peng" /> Despite TRPA being named for ankyrin repeats, TRPN channels are thought to have the most of any TRP channel, typically around 28, which are highly conserved across taxa <ref name="Schuler" /> Since its discovery, ''Drosophila'' nompC has been implicated in mechanosensation (including mechanical stimulation of the cuticle and sound detection) and cold [[nociception]].<ref name="Himmel_InvNoc">{{cite book | vauthors =Himmel N, Patel A, Cox D | chapter = Invertebrate Nociception | title = The Oxford Research Encyclopedia of Neuroscience |date=March 2017 |doi=10.1093/acrefore/9780190264086.013.166 |isbn=9780190264086 }}</ref>

===TRPP===
{| class="wikitable"
!Family
!Sub-Family<ref name="Peng" /><ref name="Montell_2001" /><ref name="Gallio_Brivido">{{cite journal | vauthors = Gallio M, Ofstad TA, Macpherson LJ, Wang JW, Zuker CS | title = The coding of temperature in the Drosophila brain | journal = Cell | volume = 144 | issue = 4 | pages = 614–24 | date = February 2011 | pmid = 21335241 | pmc = 3336488 | doi = 10.1016/j.cell.2011.01.028 | doi-access = free }}</ref><ref name="TRP_review">{{cite journal | vauthors = Himmel NJ, Cox DN | title = Transient receptor potential channels: current perspectives on evolution, structure, function and nomenclature | journal = Proceedings. Biological Sciences | volume = 287 | issue = 1933 | pages = 20201309 | date = August 2020 | pmid = 32842926 | pmc = 7482286 | doi = 10.1098/rspb.2020.1309 | doi-access = free }}</ref>
!Known Taxa<ref name="BC 2018">{{cite journal | vauthors = Bezares-Calderón LA, Berger J, Jasek S, Verasztó C, Mendes S, Gühmann M, Almeda R, Shahidi R, Jékely G | display-authors = 6 | title = Neural circuitry of a polycystin-mediated hydrodynamic startle response for predator avoidance | journal = eLife | volume = 7 | date = December 2018 | pmid = 30547885 | pmc = 6294549 | doi = 10.7554/eLife.36262 | doi-access = free }}</ref><ref name="Gallio_Brivido" />
|-
|rowspan="3" |TRPP
|PKD1-like
|Animals (excluding arthropods)
|-
|PKD2-like
|Animals
|-
|Brividos
|Insects
|}
[[TRPP]], P for "polycistin", is named for [[Autosomal dominant polycystic kidney disease|polycystic kidney disease]], which is associated with these channels.<ref name=":4" /> These channels are also referred to as PKD (polycistic kidney disease) ion channels.

PKD2-like genes (examples include [[TRPP2]], [[TRPP3]], and [[TRPP5]]) encode canonical TRP channels.  PKD1-like genes encode much larger proteins with 11 transmembrane segments, which do not have all the features of other TRP channels.  However, 6 of the transmebrane segments of PKD1-like proteins have substantial sequence homology with TRP channels, indicating they may simply have diversified greatly from other closely related proteins.<ref name="BC 2018" />

Insects have a third sub-family of TRPP, called brividos, which participate in cold sensing.<ref name="Gallio_Brivido" /><ref name="TRP_review" />

===TRPS===
TRPS, S for Soromelastatin, was named as it forms a sister group to TRPM. TRPS is broadly present in animals, but notably absent in vertebrates and insects (among others).<ref name="Himmel2" /> TRPS has not yet been well described functionally, though it is known that the ''C. elegans'' TRPS, known as CED-11, is a calcium channel which participates in [[apoptosis]].<ref>{{cite journal | vauthors = Driscoll K, Stanfield GM, Droste R, Horvitz HR | title = Presumptive TRP channel CED-11 promotes cell volume decrease and facilitates degradation of apoptotic cells in ''Caenorhabditis elegans'' | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 33 | pages = 8806–8811 | date = August 2017 | pmid = 28760991 | pmc = 5565440 | doi = 10.1073/pnas.1705084114 | doi-access = free | bibcode = 2017PNAS..114.8806D }}</ref>

===TRPV===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa <ref name="Peng" /><ref>{{cite journal | vauthors = Cattaneo AM, Bengtsson JM, Montagné N, Jacquin-Joly E, Rota-Stabelli O, Salvagnin U, Bassoli A, Witzgall P, Anfora G | display-authors = 6 | title = TRPA5, an Ankyrin Subfamily Insect TRP Channel, is Expressed in Antennae of Cydia pomonella (Lepidoptera: Tortricidae) in Multiple Splice Variants | journal = Journal of Insect Science | volume = 16 | issue = 1 | pages = 83 | date = 2016 | pmid = 27638948 | pmc = 5026476 | doi = 10.1093/jisesa/iew072 }}</ref>
|-
|rowspan="8" |TRPV
|[[Nanchung]]
|rowspan="2" |[[Placozoans]], cnidarians, nematodes, annelids, molluscs, and arthropods (possibly excluding [[arachnids]])
|-
|[[Inactive]]
|-
|[[TRPV1]]
|rowspan="6" |Specific to vertebrates
|-
|[[TRPV2]]
|-
|[[TRPV3]]
|-
|[[TRPV4]]
|-
|[[TRPV5]]
|-
|[[TRPV6]]
|-
|}
TRPV, V for "vanilloid", was originally discovered in ''Caenorhabditis elegans'', and is named for the vanilloid chemicals that activate some of these channels.<ref name="Montell_2001">{{cite journal | vauthors = Montell C | title = Physiology, phylogeny, and functions of the TRP superfamily of cation channels | journal = Science's STKE | volume = 2001 | issue = 90 | pages = re1 | date = July 2001 | pmid = 11752662 | doi = 10.1126/stke.2001.90.re1 | s2cid = 37074808 }}</ref><ref>{{cite journal | vauthors = Colbert HA, Smith TL, Bargmann CI | title = OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans | journal = The Journal of Neuroscience | volume = 17 | issue = 21 | pages = 8259–69 | date = November 1997 | pmid = 9334401 | pmc = 6573730 | doi = 10.1523/JNEUROSCI.17-21-08259.1997 }}</ref> These channels have been made famous for their association with molecules such as [[capsaicin]] (a TRPV1 agonist).<ref name=":3" />  In addition to the 6 known vertebrate paralogues, 2 major clades are known outside of the deterostomes: nanchung and Iav. Mechanistic studies of these latter clades have been largely restricted to ''Drosophila'', but phylogenetic analyses has placed a number of other genes from Placozoa, Annelida, Cnidaria, Mollusca, and other arthropods within them.<ref name="Peng" /><ref>{{cite journal | vauthors = Gong Z, Son W, Chung YD, Kim J, Shin DW, McClung CA, Lee Y, Lee HW, Chang DJ, Kaang BK, Cho H, Oh U, Hirsh J, Kernan MJ, Kim C | display-authors = 6 | title = Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing in Drosophila | journal = The Journal of Neuroscience | volume = 24 | issue = 41 | pages = 9059–66 | date = October 2004 | pmid = 15483124 | pmc = 6730075 | doi = 10.1523/JNEUROSCI.1645-04.2004 }}</ref><ref>{{cite journal | vauthors = Kim J, Chung YD, Park DY, Choi S, Shin DW, Soh H, Lee HW, Son W, Yim J, Park CS, Kernan MJ, Kim C | display-authors = 6 | title = A TRPV family ion channel required for hearing in Drosophila | journal = Nature | volume = 424 | issue = 6944 | pages = 81–4 | date = July 2003 | pmid = 12819662 | doi = 10.1038/nature01733 | s2cid = 4426696 | bibcode = 2003Natur.424...81K }}</ref> TRPV channels have also been described in protists.<ref name="Peng" />

===TRPVL===
TRPVL has been proposed to be a sister clade to TRPV, and is limited to the cnidarians ''[[Nematostella vectensis]]'' and ''[[Hydra magnipapillata]]'', and the annelid ''[[Capitella teleta]]''.<ref name="Peng" /> Little is known concerning these channels.

===TRPY===
TRPY, Y for "yeast", is highly localized to the yeast vacuole, which is the functional equivalent of a lysosome in a mammalian cell, and acts as a mechanosensor for vacuolar osmotic pressure. Patch clamp techniques and hyperosmotic stimulation have illustrated that TRPY plays a role in intracellular calcium release.<ref>{{cite journal | vauthors = Dong XP, Wang X, Xu H | title = TRP channels of intracellular membranes | journal = Journal of Neurochemistry | volume = 113 | issue = 2 | pages = 313–28 | date = April 2010 | pmid = 20132470 | pmc = 2905631 | doi = 10.1111/j.1471-4159.2010.06626.x }}</ref> Phylogenetic analysis has shown that TRPY1 does not form a part with the other metazoan TRP groups one and two, and is suggested to have evolved after the divergence of metazoans and fungi.<ref name="Kadowaki_evodyn"/> Others have indicated that TRPY are more closely related to TRPP.<ref>{{cite journal | vauthors = Palovcak E, Delemotte L, Klein ML, Carnevale V | title = Comparative sequence analysis suggests a conserved gating mechanism for TRP channels | journal = The Journal of General Physiology | volume = 146 | issue = 1 | pages = 37–50 | date = July 2015 | pmid = 26078053 | pmc = 4485022 | doi = 10.1085/jgp.201411329 }}</ref>

== Structure ==
TRP channels are composed of 6 [[Cell membrane|membrane]]-spanning helices (S1-S6) with intracellular [[N-terminus|N-]] and [[C terminus|C-termini]]. Mammalian TRP channels are activated and regulated by a wide variety of stimuli including many post-transcriptional mechanisms like [[phosphorylation]], [[G protein-coupled receptor|G-protein receptor coupling]], ligand-gating, and [[ubiquitin]]ation. The receptors are found in almost all cell types and are largely localized in cell and organelle membranes, modulating ion entry.

Most TRP channels form homo- or heterotetramers when completely functional. The ion selectivity filter, pore, is formed by the complex combination of p-loops in the tetrameric protein, which are situated in the extracellular domain between the S5 and S6 transmembrane segments. As with most cation channels, TRP channels have negatively charged residues within the pore to attract the positively charged ions.<ref>{{Cite book|title=Ion channels of excitable membranes| vauthors = Hille B |date=2001|publisher=Sinauer|isbn=978-0878933211|edition= 3rd|location=Sunderland, Mass.|oclc=46858498}}</ref>

=== Group 1 Characteristics ===
Each channel in this group is structurally unique, which adds to the diversity of functions that TRP channels possess, however, there are some commonalities that distinguish this group from others. Starting from the intracellular N-terminus there are varying lengths of ankryin repeats (except in TRPM) that aid with membrane anchoring and other protein interactions. Shortly following S6 on the C-terminal end, there is a highly conserved TRP domain (except in TRPA) which is involved with gating modulation and channel multimerization. Other C-terminal modifications such as alpha-kinase domains in TRPM7 and M8 have been seen as well in this group.<ref name="Kadowaki_evodyn"/><ref name=":3" /><ref name=":4" />

=== Group 2 Characteristics ===
Group two most distinguishable trait is the long extracellular span between the S1 and S2 transmembrane segments. Members of group two are also lacking in ankryin repeats and a TRP domain. They have been shown, however, to have endoplasmic reticulum (ER) retention sequences towards on the C-terminal end illustrating possible interactions with the ER.<ref name="Kadowaki_evodyn"/><ref name=":3" /><ref name=":4" />

== Function ==
TRP channels modulate ion entry driving forces and Ca<sup>2+</sup> and Mg<sup>2+</sup> transport machinery in the plasma membrane, where most of them are located.  TRPs have important interactions with other proteins and often form signaling complexes, the exact pathways of which are unknown.<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 name="pmid5344615"/> which displayed transient elevation of potential in response to light stimuli and were so named ''transient receptor potential'' channels.<ref name="pmid2516726">{{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> TRPML channels function as intracellular calcium release channels and thus serve an important role in organelle regulation.<ref name="pmid3129667"/> Importantly, many of these channels mediate a variety of sensations like the sensations of pain, temperature, different kinds of taste, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and are used in animals to sense hot or cold. TRPs act as sensors of [[osmotic pressure]], [[volume]], [[Stretching|stretch]], and [[vibration]]. TRPs have been seen to have complex multidimensional roles in sensory signaling. Many TRPs function as intracellular calcium release channels.

=== Pain and temperature sensation ===
TRP ion channels convert energy into action potentials in somatosensory nociceptors.<ref name="pmid2683630">
{{cite journal | vauthors = Eccles R | title = Nasal physiology and disease with reference to asthma | journal = Agents and Actions. Supplements | volume = 28 | pages = 249–61 | year = 1989 | pmid = 2683630 }}</ref>  Thermo-TRP channels have a C-terminal domain that is responsible for [[thermosensation]] and have a specific interchangeable region that allows them to sense temperature stimuli that is tied to ligand regulatory processes.<ref>
{{cite journal | vauthors = Brauchi S, Orta G, Salazar M, Rosenmann E, Latorre R | title = A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels | journal = The Journal of Neuroscience | volume = 26 | issue = 18 | pages = 4835–40 | date = May 2006 | pmid = 16672657 | pmc = 6674176 | doi = 10.1523/JNEUROSCI.5080-05.2006 }}</ref>  Although most TRP channels are modulated by changes in temperature, some have a crucial role in temperature sensation. There are at least 6 different Thermo-TRP channels and each plays a different role.  For instance, [[TRPM8]] relates to mechanisms of sensing cold, [[TRPV1]] and [[TRPM3]] contribute to heat and inflammation sensations, and [[TRPA1]] facilitates many signaling pathways like sensory transduction, [[nociception]], [[inflammation]] and [[oxidative stress]].<ref name="pmid2683630"/>

=== Taste ===
TRPM5 is involved in [[taste]] signaling of [[sweet]], [[bitter (taste)|bitter]] and [[umami]] tastes by modulating the signal pathway in type II [[taste receptor]] cells.<ref>{{cite journal | vauthors = Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, Pinto S, Segal A, Antoine N, Gysemans C, Laureys J, Lemaire K, Gilon P, Cuypers E, Tytgat J, Mathieu C, Schuit F, Rorsman P, Talavera K, Voets T, Vennekens R | display-authors = 6 | title = Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity | journal = Nature Communications | volume = 8 | pages = 14733 | date = March 2017 | pmid = 28361903 | pmc = 5380970 | doi = 10.1038/ncomms14733 | bibcode = 2017NatCo...814733P }}</ref> TRPM5 is activated by the sweet glycosides found in the [[stevia rebaudiana|stevia]] plant.

Several other TRP channels play a significant role in chemosensation through sensory nerve endings in the mouth that are independent from taste buds. TRPA1 responds to mustard oil ([[allyl isothiocyanate]]), wasabi, and cinnamon, TRPA1 and TRPV1 respond to garlic ([[allicin]]), TRPV1 responds to chilli pepper ([[capsaicin]]), TRPM8 is activated by [[menthol]], [[camphor]], [[peppermint]], and cooling agents; and TRPV2 is activated by molecules ([[THC]], [[Cannabidiol|CBD]] and [[Cannabinol|CBN]]) found in marijuana.

== TRP-like channels in insect vision ==
[[Image:TRP P.Americana retina.jpg|thumb|300px|right|Figure 1. Light-activated TRPL channels in ''[[Periplaneta americana]]'' photoreceptors. A, a typical current through TRPL channels was evoked by a 4-s pulse of bright light (horizontal bar). B, a photoreceptor membrane voltage response to the light-induced activation of TRPL channels, data from the same cell are shown]]
The ''trp''-mutant fruit flies, which lack a functional copy of trp gene, are characterized by a transient response to light, unlike wild-type flies that demonstrate a sustained [[photoreceptor cell]] activity in response to light.<ref name="pmid5344615">{{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 | s2cid = 4200329 | bibcode = 1969Natur.224..285C }}</ref>
A distantly related isoform of TRP channel, TRP-like channel (TRPL), was later identified in ''Drosophila'' photoreceptors, where it is expressed at approximately 10- to 20-fold lower levels than TRP protein. A mutant fly, ''trpl'', was subsequently isolated. Apart from structural differences, the TRP and TRPL channels differ in cation permeability and pharmacological properties.
 
TRP/TRPL channels are solely responsible for depolarization of insect photoreceptor plasma membrane in response to light. When these channels open, they allow sodium and calcium to enter the cell down the concentration gradient, which depolarizes the membrane. Variations in light intensity affect the total number of open TRP/TRPL channels, and, therefore, the degree of membrane depolarization. These graded voltage responses propagate to photoreceptor [[synapse]]s with second-order retinal [[neuron]]s and further to the brain.

It is important to note that the mechanism of insect photoreception is dramatically different from that in mammals. Excitation of rhodopsin in mammalian photoreceptors leads to the hyperpolarization of the receptor membrane but not to depolarization as in the insect eye. In ''Drosophila'' and, it is presumed, other insects, a phospholipase C (PLC)-mediated signaling cascade links photoexcitation of [[rhodopsin]] to the opening of the TRP/TRPL channels.  Although numerous activators of these channels such as phosphatidylinositol-4,5-bisphosphate (PIP<sub>2</sub>) and polyunsaturated fatty acids (PUFAs) were known for years, a key factor mediating chemical coupling between PLC and TRP/TRPL channels remained a mystery until recently. It was found that breakdown of a lipid product of PLC cascade, diacylglycerol (DAG), by the enzyme [[diacylglycerol lipase]], generates PUFAs that can activate TRP channels, thus initiating membrane depolarization in response to light.<ref>{{cite journal | vauthors = Leung HT, Tseng-Crank J, Kim E, Mahapatra C, Shino S, Zhou Y, An L, Doerge RW, Pak WL | display-authors = 6 | title = DAG lipase activity is necessary for TRP channel regulation in Drosophila photoreceptors | journal = Neuron | volume = 58 | issue = 6 | pages = 884–96 | date = June 2008 | pmid = 18579079 | pmc = 2459341 | doi = 10.1016/j.neuron.2008.05.001 }}</ref> This mechanism of TRP channel activation may be well-preserved among other cell types where these channels perform various functions.

== 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, TRPV3 and TRPM8’s role as thermoreceptors, and TRPV4 and TRPA1’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 | doi-access = free }}</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 | doi-access = free }}</ref> The TRPV1 agonist capsaicin, found in chili peppers, has been indicated to relieve neuropathic pain.<ref name="pmid3129667"/>   TRPV1 agonists inhibit nociception at TRPV1

=== Role in cancer ===
Altered expression of TRP proteins often leads to [[tumorigenesis]], as reported for TRPV1, TRPV6, TRPC1, TRPC6, TRPM4, TRPM5, and TRPM8.<ref name="pmid17616360"/> TRPV1 and TRPV2 have been implicated in breast cancer. TRPV1 expression in aggregates found at [[endoplasmic reticulum]] or [[Golgi apparatus]] and/or surrounding these structures in breast cancer patients confer worse survival.<ref>{{cite journal | vauthors = Lozano C, Córdova C, Marchant I, Zúñiga R, Ochova P, Ramírez-Barrantes R, González-Arriagada WA, Rodriguez B, Olivero P | display-authors = 6 | title = Intracellular aggregated TRPV1 is associated with lower survival in breast cancer patients | journal = Breast Cancer: Targets and Therapy| volume = 10 | pages = 161–168 | date = 15 October 2018 | pmid = 30410392 | pmc = 6197232 | doi = 10.2147/BCTT.S170208 | doi-access = free }}</ref>

TRPM family of ion channels are particularly associated with prostate cancer where TRPM2 (and its long noncoding RNA ''TRPM2-AS''), TRPM4, and TRPM8 are overexpressed in prostate cancer associated with more aggressive outcomes.<ref>{{cite journal | vauthors = Wong KK, Banham AH, Yaacob NS, Nur Husna SM | title = The oncogenic roles of TRPM ion channels in cancer | journal = Journal of Cellular Physiology | volume = 234 | issue = 9 | pages = 14556–14573 | date = February 2019 | pmid = 30710353 | doi = 10.1002/jcp.28168 | s2cid = 73432591 | url = https://ora.ox.ac.uk/objects/uuid:fabb30b0-db58-46b5-b4d6-8c7b82a36147 | url-access = subscription }}</ref> TRPM3 has been shown to promote growth and [[autophagy]] in clear cell renal cell carcinoma,<ref>{{cite journal | vauthors = Hall DP, Cost NG, Hegde S, Kellner E, Mikhaylova O, Stratton Y, Ehmer B, Abplanalp WA, Pandey R, Biesiada J, Harteneck C, Plas DR, Meller J, Czyzyk-Krzeska MF | display-authors = 6 | title = TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma | journal = Cancer Cell | volume = 26 | issue = 5 | pages = 738–53 | date = November 2014 | pmid = 25517751 | pmc = 4269832 | doi = 10.1016/j.ccell.2014.09.015 }}</ref> TRPM4 is overexpressed in [[diffuse large B-cell lymphoma]] associated with poorer survival,<ref>{{cite journal | vauthors = Loo SK, Ch'ng ES, Md Salleh MS, Banham AH, Pedersen LM, Møller MB, Green TM, Wong KK | display-authors = 6 | title = TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma | journal = Histopathology | volume = 71 | issue = 1 | pages = 98–111 | date = July 2017 | pmid = 28248435 | doi = 10.1111/his.13204 | s2cid = 4767956 | url = https://ora.ox.ac.uk/objects/uuid:5ea94e06-3bbd-4e08-b202-68e0757453f9 | url-access = subscription }}</ref> while TRPM5 has oncogenic properties in [[melanoma]].<ref>{{cite journal | vauthors = Palmer RK, Atwal K, Bakaj I, Carlucci-Derbyshire S, Buber MT, Cerne R, Cortés RY, Devantier HR, Jorgensen V, Pawlyk A, Lee SP, Sprous DG, Zhang Z, Bryant R | display-authors = 6 | title = Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel | journal = Assay and Drug Development Technologies | volume = 8 | issue = 6 | pages = 703–13 | date = December 2010 | pmid = 21158685 | doi = 10.1089/adt.2010.0334 }}</ref>

TRP channels take center stage in modulating [[chemotherapy]] resistance in breast cancer.<ref name=Chemo>{{cite journal |last1=Soussi |first1=M |last2=Hasselsweiller |first2=A |last3=Gkika |first3=D |title=TRP Channels: The Neglected Culprits in Breast Cancer Chemotherapy Resistance? |journal=Membranes |date=12 September 2023 |volume=13 |issue=9 |page=788 |doi=10.3390/membranes13090788 |doi-access=free |pmid=37755210 |pmc=10536409}} {{CC-notice|cc=by4}}</ref> Some TRP channels such as TRPA1 and TRPC5 are tightly associated with drug resistance during cancer treatment; TRPC5-mediated high Ca<sup>2+</sup> influx activates the transcription factor [[NFAT|NFATC3]] (Nuclear Factor of Activated T Cells, Cytoplasmic 3), which triggers [[p-glycoprotein]] (p-gp) transcription. The overexpression of p-gp is widely recognized as a major factor in [[Antineoplastic resistance|chemoresistance]] in cancer cells, as it functions as an active efflux pump that can remove various foreign substances, including chemotherapeutic agents, from within the cell.<ref name="Chemo" />
[[File:TRPC5 Chemo.jpg|upright=1.3|thumb|TRPC5-mediated chemoresistance:<ol type="a">
<li>TRPC5 overexpression activates the transcription factor NFATC3 Ca<sup>2+</sup> signaling pathway, leading to p-gp overexpression. Moreover, the overexpressed p-gp expels chemotherapeutic drugs such as [[doxorubicin]] triggering chemoresistance.</li>
<li>Chemoresistant breast cancer cells overexpressing TRPC5 transfer channel units to chemo sensitive recipient cells via [[extracellular vesicles]] (EV), leading to the development of TRPC5-mediated chemoresistance in these cells.<ref name="Chemo" /></li>
</ol>]]
Contrarily, other TRP channels, such as TRPV1 and TRPV2, have been demonstrated to potentiate the anti-tumorigenic effects of certain chemotherapeutic agents and TRPV2 is a potential biomarker and therapeutic target in triple negative breast cancer.<ref name="Chemo" />

=== Role in inflammatory responses ===
In addition to [[TLR4]] mediated pathways, certain members of the family of the transient receptor potential ion channels recognize [[Lipopolysaccharide|LPS]]. LPS-mediated activation of TRPA1 was shown in mice<ref>{{cite journal | vauthors = Meseguer V, Alpizar YA, Luis E, Tajada S, Denlinger B, Fajardo O, Manenschijn JA, Fernández-Peña C, Talavera A, Kichko T, Navia B, Sánchez A, Señarís R, Reeh P, Pérez-García MT, López-López JR, Voets T, Belmonte C, Talavera K, Viana F | display-authors = 6 | title = TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins | journal = Nature Communications | volume = 5 | pages = 3125 | date = 20 January 2014 | pmid = 24445575 | pmc = 3905718 | doi = 10.1038/ncomms4125 | bibcode = 2014NatCo...5.3125M }}</ref> and ''Drosophila melanogaster'' flies.<ref>{{cite journal | vauthors = Soldano A, Alpizar YA, Boonen B, Franco L, López-Requena A, Liu G, Mora N, Yaksi E, Voets T, Vennekens R, Hassan BA, Talavera K | display-authors = 6 | title = Gustatory-mediated avoidance of bacterial lipopolysaccharides via TRPA1 activation in Drosophila | journal = eLife | volume = 5 | date = June 2016 | pmid = 27296646 | pmc = 4907694 | doi = 10.7554/eLife.13133 | doi-access = free }}</ref> At higher concentrations, LPS activates other members of the sensory TRP channel family as well, such as TRPV1, TRPM3 and to some extent TRPM8.<ref>{{cite journal | vauthors = Boonen B, Alpizar YA, Sanchez A, López-Requena A, Voets T, Talavera K | title = Differential effects of lipopolysaccharide on mouse sensory TRP channels | journal = Cell Calcium | volume = 73 | pages = 72–81 | date = July 2018 | pmid = 29689522 | doi = 10.1016/j.ceca.2018.04.004 | s2cid = 13681499 | url = https://lirias.kuleuven.be/handle/123456789/623401 | url-access = subscription }}</ref> LPS is recognized by TRPV4 on epithelial cells. TRPV4 activation by LPS was necessary and sufficient to induce nitric oxide production with a bactericidal effect.<ref>{{cite journal | vauthors = Alpizar YA, Boonen B, Sanchez A, Jung C, López-Requena A, Naert R, Steelant B, Luyts K, Plata C, De Vooght V, Vanoirbeek JA, Meseguer VM, Voets T, Alvarez JL, Hellings PW, Hoet PH, Nemery B, Valverde MA, Talavera K | display-authors = 6 | title = TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells | journal = Nature Communications | volume = 8 | issue = 1 | pages = 1059 | date = October 2017 | pmid = 29057902 | pmc = 5651912 | doi = 10.1038/s41467-017-01201-3 | bibcode = 2017NatCo...8.1059A }}</ref>

==History of ''Drosophila'' TRP channels==
The original TRP-mutant in ''Drosophila'' was first described by Cosens and Manning in 1969 as "a mutant strain of ''D. melanogaster'' which, though behaving phototactically positive in a T-maze under low ambient light, is visually impaired and behaves as though blind". It also showed an abnormal [[electroretinogram]] response of [[Simple eye in invertebrates|photoreceptor]]s to light which was transient rather than sustained as in the "wild type".<ref name="pmid5344615"/> It was investigated subsequently by Baruch Minke, a post-doc in the group of William Pak, and named TRP according to its behavior in the ERG.<ref name="pmid810728">{{cite journal | vauthors = Minke B, Wu C, Pak WL | title = Induction of photoreceptor voltage noise in the dark in Drosophila mutant | journal = Nature | volume = 258 | issue = 5530 | pages = 84–7 | date = November 1975 | pmid = 810728 | doi = 10.1038/258084a0 | s2cid = 4206531 | bibcode = 1975Natur.258...84M }}</ref> The identity of the mutated protein was unknown until it was cloned by Craig Montell, a post-doctoral researcher in Gerald Rubin's research group, in 1989, who noted its predicted structural relationship to channels known at the time<ref name="pmid2516726"/> and Roger Hardie and Baruch Minke who provided evidence in 1992 that it is an ion channel that opens in response to light stimulation.<ref name="pmid1314617">{{cite journal | vauthors = Hardie RC, Minke B | title = The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors | journal = Neuron | volume = 8 | issue = 4 | pages = 643–51 | date = April 1992 | pmid = 1314617 | doi = 10.1016/0896-6273(92)90086-S | s2cid = 34820827 }}</ref> The TRPL channel was cloned and characterized in 1992 by the research group of Leonard Kelly.<ref name="pmid1314616">{{cite journal | vauthors = Phillips AM, Bull A, Kelly LE | title = Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene | journal = Neuron | volume = 8 | issue = 4 | pages = 631–42 | date = April 1992 | pmid = 1314616 | doi = 10.1016/0896-6273(92)90085-R | s2cid = 21130927 }}</ref> In 2013, Montell and his research group found that the TRPL (TRP-like) cation channel was a direct target for tastants in gustatory receptor neurons and could be reversibly down-regulated.<ref>{{Cite journal |last1=Zhang |first1=Yali V. |last2=Raghuwanshi |first2=Rakesh P. |last3=Shen |first3=Wei L. |last4=Montell |first4=Craig |date=October 2013 |title=Food experience-induced taste desensitization modulated by the Drosophila TRPL channel |journal=Nature Neuroscience |volume=16 |issue=10 |pages=1468–1476 |doi=10.1038/nn.3513 |issn=1546-1726 |pmc=3785572 |pmid=24013593}}</ref>

== See also ==
* [[Endocannabinoid system]]
* [[Transient receptor potential channel-interacting protein database]] (2010)<!--- Place in SA section for now, may need to be moved into another part of article, expert help needed. --->

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

== External links ==
* {{MeshName|Transient+Receptor+Potential+Channels}}
{{Refbegin}}
* {{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.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=78 | title = Transient Receptor Potential channels | vauthors = Clapham DE, DeCaen P, Carvacho I, Chaudhuri D, Doerner JF, Julius D, Kahle KT, McKemy D, Oancea E, Sah R, Stotz SC, Tong D, Wu LJ, Xu H, Nilius B, Owsianik G | display-authors = 6 | publisher = IUPHAR/BPS Guide to Pharmacology }}
* {{cite web | url = http://www.trpchannel.org | title = TRIP Database | work = a manually curated database of protein-protein interactions for mammalian TRP channels }}
{{Refend}}

{{Ion channels|g4}}
{{Transient receptor potential channel modulators}}
{{Authority control}}

[[Category:Membrane biology]]
[[Category:Ion channels]]
[[Category:Voltage-gated ion channels]]