TRPM5

TRPM5
Identifiers
Aliases	TRPM5 , LTRPC5, MTR1, transient receptor potential cation channel subfamily M member 5
External IDs	OMIM: 604600; MGI: 1861718; HomoloGene: 22818; GeneCards: TRPM5; OMA:TRPM5 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11p15.5 Start 2,404,515 bp [1] End 2,444,514 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 F5 Start 142,622,890 bp [2] End 142,648,379 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon seminal vesicula body of pancreas duodenum metanephros left lobe of thyroid gland epididymis right lobe of thyroid gland caput epididymis left adrenal cortex Top expressed in islet of Langerhans internal carotid artery urethra female urethra male urethra efferent ductule external carotid artery Gonadal ridge vas deferens intestinal villus More reference expression data BioGPS n/a
Gene ontology Molecular function voltage-gated ion channel activity ion channel activity potassium channel activity calcium activated cation channel activity sodium channel activity Cellular component plasma membrane membrane soma dendrite integral component of membrane Biological process ion transport sodium ion transmembrane transport sensory perception of taste calcium ion transmembrane transport potassium ion transmembrane transport cation transport regulation of ion transmembrane transport ion transmembrane transport transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 29850 56843 Ensembl ENSG00000070985 ENSMUSG00000009246 UniProt Q9NZQ8 Q9JJH7 RefSeq (mRNA) NM_014555 NM_020277 RefSeq (protein) NP_055370 NP_064673 Location (UCSC) Chr 11: 2.4 – 2.44 Mb Chr 7: 142.62 – 142.65 Mb PubMed search [3] [4]
Wikidata
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Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene. ^{[5] [6]}

Function

TRPM5 is a calcium-activated non-selective cation channel that induces depolarization upon increases in intracellular calcium, it is a signal mediator in chemosensory cells. Channel activity is initiated by a rise in the intracellular calcium, and the channel permeates monovalent cations as K⁺ and Na⁺. TRPM5 is a key component of taste transduction in the gustatory system of bitter, sweet and umami tastes being activated by high levels of intracellular calcium. It has also been targeted as a possible contributor to fat taste signaling. ^{[7] [8]} The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an action potential. ^[9]

TRPM5 is expressed in pancreatic β-cells ^[10] where it is involved in the signaling mechanism for insulin secretion. The potentiation of TRPM5 in the β-cells leads to increased insulin secretion and protects against the development of type 2 diabetes in mice. ^[11] Further expression of TRPM5 can be found in tuft cells, ^[12] solitary chemosensory cells and several other cell types in the body that have a sensory role.

Drugs modulating TRPM5

The role of TRPM5 in the pancreatic β-cell makes it a target for the development of novel antidiabetic therapies. ^[13]

Agonists

• Steviol glycosides, the sweet compounds in the leaves of the Stevia rebaudiana plant, potentiate the calcium-induced activity of TRPM5. In this way they stimulate the glucose-induced insulin secretion from the pancreatic β-cell. ^[11]
• Rutamarin, a phytochemical found in Ruta graveolens has been identified as an activator of several TRP channels, including TRPM5 and TRPV1 and inhibits the activity of TRPM8. ^[14]

Antagonists

Selective blocking agents of TRPM5 ion channels can be used to identify TRPM5 currents in primary cells. Most identified compounds show, however, a poor selectivity between TRPM4 and TRPM5 or other ion channels.

• TPPO or TriPhenylPhosphineOxide is the most selective blocker of TRPM5 however, its application suffers due to a poor solubility. ^[15]
• Ketoconazole is an antifungal drug that inhibits TRPM5 activity. ^[16]
• Flufenamic Acid is an NSAID drug that inhibits the activity of TRPM5 or TRPM4. ^[17]
• Clotrimazole is an antifungal drug and reduces the currents through TRPM5. ^[17]
• Nicotine inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained. ^[18]

See also

• TRPM

References

1. GRCh38: Ensembl release 89: ENSG00000070985 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000009246 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Prawitt D, Enklaar T, Klemm G, Gärtner B, Spangenberg C, Winterpacht A, et al. (January 2000). "Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression". Human Molecular Genetics. 9 (2): 203–216. doi: 10.1093/hmg/9.2.203 . PMID   10607831.
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): 427–450. doi:10.1124/pr.57.4.6. PMID   16382100. S2CID   17936350.
7. Mattes RD (September 2011). "Accumulating evidence supports a taste component for free fatty acids in humans". Physiology & Behavior. 104 (4): 624–631. doi:10.1016/j.physbeh.2011.05.002. PMC   3139746 . PMID   21557960.
8. Liu P, Shah BP, Croasdell S, Gilbertson TA (June 2011). "Transient receptor potential channel type M5 is essential for fat taste". The Journal of Neuroscience : The Official Journal of the Society for Neuroscience. 31 (23): 8634–8642. doi:10.1523/JNEUROSCI.6273-10.2011. PMC   3125678 . PMID   21653867.
9. Chaudhari N, Roper SD (August 2010). "The cell biology of taste". The Journal of Cell Biology. 190 (3): 285–296. doi:10.1083/jcb.201003144. PMC   2922655 . PMID   20696704.
10. Colsoul B, Schraenen A, Lemaire K, Quintens R, Van Lommel L, Segal A, et al. (March 2010). "Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice". Proceedings of the National Academy of Sciences of the United States of America. 107 (11): 5208–5213. Bibcode:2010PNAS..107.5208C. doi: 10.1073/pnas.0913107107 . PMC   2841940 . PMID   20194741.
11. Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, et al. (March 2017). "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications. 8: 14733. Bibcode:2017NatCo...814733P. doi:10.1038/ncomms14733. PMC   5380970 . PMID   28361903.
12. Kaske S, Krasteva G, König P, Kummer W, Hofmann T, Gudermann T, et al. (July 2007). "TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells". BMC Neuroscience. 8: 49. doi: 10.1186/1471-2202-8-49 . PMC   1931605 . PMID   17610722.
13. Philippaert K, Vennekens R (1 January 2015). "Transient Receptor Potential (TRP) Cation Channels in Diabetes". Chapter 19 - Transient Receptor Potential (TRP) Cation Channels in Diabetes. pp. 343–363. doi:10.1016/B978-0-12-420024-1.00019-9. ISBN   978-0-12-420024-1.{{cite book}}: |journal= ignored (help)
14. Mancuso G, Borgonovo G, Scaglioni L, Bassoli A (October 2015). "Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception". Molecules. 20 (10). Basel, Switzerland: 18907–18922. doi: 10.3390/molecules201018907 . PMC   6331789 . PMID   26501253.
15. Palmer RK, Atwal K, Bakaj I, Carlucci-Derbyshire S, Buber MT, Cerne R, et al. (December 2010). "Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel". Assay and Drug Development Technologies. 8 (6): 703–713. doi:10.1089/adt.2010.0334. PMID   21158685.
16. Philippaert K, Kerselaers S, Voets T, Vennekens R (January 2018). "2+-Activated Monovalent Cation-Selective Channels". SLAS Discovery : Advancing Life Sciences R & D. 23 (4): 341–352. doi: 10.1177/2472555217748932 . PMID   29316407.
17. Ullrich ND, Voets T, Prenen J, Vennekens R, Talavera K, Droogmans G, et al. (March 2005). "Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice". Cell Calcium. 37 (3): 267–278. doi:10.1016/j.ceca.2004.11.001. PMID   15670874.
18. Gees M, Alpizar YA, Luyten T, Parys JB, Nilius B, Bultynck G, et al. (May 2014). "Differential effects of bitter compounds on the taste transduction channels TRPM5 and IP3 receptor type 3". Chemical Senses. 39 (4): 295–311. doi: 10.1093/chemse/bjt115 . PMID   24452633.

Further reading

• Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, et al. (March 2017). "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications. 8: 14733. Bibcode:2017NatCo...814733P. doi:10.1038/ncomms14733. PMC   5380970 . PMID   28361903.
• Islam MS (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. Berlin: Springer. p. 700. ISBN   978-94-007-0264-6.
• Liman ER (2007). "TRPM5 and Taste Transduction". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. Vol. 179. pp. 287–298. doi:10.1007/978-3-540-34891-7_17. ISBN   978-3-540-34889-4. PMID   17217064.
• Holzer P (July 2011). "Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system". Pharmacology & Therapeutics. 131 (1): 142–170. doi:10.1016/j.pharmthera.2011.03.006. PMC   3107431 . PMID   21420431.
• Boesmans W, Owsianik G, Tack J, Voets T, Vanden Berghe P (January 2011). "TRP channels in neurogastroenterology: opportunities for therapeutic intervention". British Journal of Pharmacology. 162 (1): 18–37. doi:10.1111/j.1476-5381.2010.01009.x. PMC   3012403 . PMID   20804496.
• Liman ER (2010). "Changing Taste by Targeting the Ion Channel TRPM5". The Open Drug Discovery Journal. 2: 98–102. doi: 10.2174/1875039701407010001 .
• Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, et al. (June 2010). "TRPM5 regulates glucose-stimulated insulin secretion". Pflügers Archiv : European Journal of Physiology. 460 (1): 69–76. doi:10.1007/s00424-010-0835-z. PMC   5663632 . PMID   20393858.
• Oliveira-Maia AJ, Stapleton-Kotloski JR, Lyall V, Phan TH, Mummalaneni S, Melone P, et al. (February 2009). "Nicotine activates TRPM5-dependent and independent taste pathways". Proceedings of the National Academy of Sciences of the United States of America. 106 (5): 1596–1601. Bibcode:2009PNAS..106.1596O. doi: 10.1073/pnas.0810184106 . PMC   2635785 . PMID   19164511.
• Liu D, Zhang Z, Liman ER (May 2005). "Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains". The Journal of Biological Chemistry. 280 (21): 20691–20699. doi: 10.1074/jbc.M414072200 . PMID   15731110.
• Liu D, Liman ER (December 2003). "Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5". Proceedings of the National Academy of Sciences of the United States of America. 100 (25): 15160–15165. Bibcode:2003PNAS..10015160L. doi: 10.1073/pnas.2334159100 . PMC   299934 . PMID   14657398.
• Wu LJ, Sweet TB, Clapham DE (September 2010). "International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family". Pharmacological Reviews. 62 (3): 381–404. doi:10.1124/pr.110.002725. PMC   2964900 . PMID   20716668.

External links

• TRPM5+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• IUPHAR Archived 2012-10-16 at the Wayback Machine
• HGNC Gene families Archived 2013-09-20 at the Wayback Machine
• Pfam

This article incorporates text from the United States National Library of Medicine, which is in the public domain.