TRPM3

Last updated
TRPM3
Identifiers
Aliases TRPM3 , GON-2, LTRPC3, MLSN2, transient receptor potential cation channel subfamily M member 3
External IDs OMIM: 608961 MGI: 2443101 HomoloGene: 62287 GeneCards: TRPM3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)

n/a

Location (UCSC) Chr 9: 70.53 – 71.45 Mb Chr 19: 22.12 – 22.97 Mb
PubMed search [3] [4]
Wikidata
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Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene. [5]

Function

The product of this gene belongs to the family of transient receptor potential (TRP) channels. [6] TRP channels are Ca2+ permeable non-selective cation channels that play roles in a wide variety of physiological processes, including calcium signaling, heat and cold sensation, calcium and magnesium homeostasis. TRPMs mediates sodium and calcium entry, which induces depolarization and a cytoplasmic Ca2+ signal. Alternatively spliced transcript variants encoding different isoforms have been -identified. [7] TRPM3 was shown to be activated by the neurosteroid pregnenolone sulfate as well as the synthetic compound CIM0216.

Peripheral heat sensation

TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia, and they are activated by high temperatures. [8] Genetic deletion of TRPM3 in mice reduces sensitivity to noxious heat, as well as inflammatory thermal hyperalgesia. [8] [9] Inhibitors of TRPM3 were also shown to reduce noxious heat and inflammatory heat hyperalgesia, [10] [11] [9] as well as reduce heat hyperalgesia and spontaneous pain in nerve injury induced neuropathic pain. [9]

Receptor mediated inhibition

TRPM3 is robustly inhibited by the activation of cell surface receptors that couple to inhibitory heterotrimeric G-proteins (Gi) via direct binding of the Gβγ subunit of the G-protein to the channel. [12] [13] [14] Gβγ was shown to bind to a short α-helical segment of the channel. [15] Receptors that inhibit TRPM3 include opioid receptors [13] [16] and GABAB receptors. [12]

TRPM3 in the brain

Mutations in TRPM3 in humans, were recently shown to cause a intellectual disability and epilepsy. [17] The disease associated mutations were shown to increase the sensitivity of the channel to agonists, and heat. [18] [19] [20]

TRPM3 ligands, activators and modulators

Activators

Channel Blockers

  1. Mefenamic acid [23]
  2. Citrus fruit flavonoids, e.g. naringenin, isosakuranetin and hesperetin, as well as ononetin (a deoxybenzoin). [24]
  3. Primidone, a clinically used antiepileptic medication also directly inhibits TRPM3. [10]

Activity Modulator

See also

Related Research Articles

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, 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. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or 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.

<span class="mw-page-title-main">TRPV1</span> Human protein for regulating body temperature

The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. And a receptor being clearly present in bacteria, the oldest organisms on Earth known to express phosphatidylethanolamine, the precursor to endocannabinoids, in their cytoplasmic membranes, and fatty acid metabolites with affinity for this CB receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA).

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

TRPM is a family of transient receptor potential ion channels (M standing for wikt:melastatin). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8.

<span class="mw-page-title-main">TRPM6</span> Protein-coding gene in the species Homo sapiens

TRPM6 is a transient receptor potential ion channel associated with hypomagnesemia with secondary hypocalcemia.

<span class="mw-page-title-main">TRPM1</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 1 is a protein that in humans is encoded by the TRPM1 gene.

<span class="mw-page-title-main">TRPC4</span> Protein and coding gene in humans

The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the TRPC4 gene.

<span class="mw-page-title-main">TRPC5</span> Protein-coding gene in the species Homo sapiens

Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the TRPC5 gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion channels.

<span class="mw-page-title-main">TRPM2</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.

<span class="mw-page-title-main">TRPA1</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the TRPA1 gene.

<span class="mw-page-title-main">TRPM5</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TRPM4</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 4 (hTRPM4), also known as melastatin-4, is a protein that in humans is encoded by the TRPM4 gene.

<span class="mw-page-title-main">TRPV4</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

<span class="mw-page-title-main">TRPM8</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

<span class="mw-page-title-main">TRPV3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily V, member 3, also known as TRPV3, is a human gene encoding the protein of the same name.

<span class="mw-page-title-main">TRPM7</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily M, member 7, also known as TRPM7, is a human gene encoding a protein of the same name.

<span class="mw-page-title-main">TRPV5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 5 is a calcium channel protein that in humans is encoded by the TRPV5 gene.

The transient receptor potential Ca2+ channel (TRP-CC) family (TC# 1.A.4) is a member of the voltage-gated ion channel (VIC) superfamily and consists of cation channels conserved from worms to humans. The TRP-CC family also consists of seven subfamilies (TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML) based on their amino acid sequence homology:

  1. the canonical or classic TRPs,
  2. the vanilloid receptor TRPs,
  3. the melastatin or long TRPs,
  4. ankyrin (whose only member is the transmembrane protein 1 [TRPA1])
  5. TRPN after the nonmechanoreceptor potential C (nonpC), and the more distant cousins,
  6. the polycystins
  7. and mucolipins.
<span class="mw-page-title-main">Ononetin</span> Chemical compound

Ononetin is a natural product from the deoxybenzoin group, which is found in the Russian traditional medicine plant Ononis spinosa. It acts as an inhibitor of the transient receptor potential ion channel TRPM3 and has analgesic effects in animal studies, as well as being used for research into the role of TRPM3 in the immune system dysfunction associated with chronic fatigue syndrome.

TRPM3-related neurodevelopmental disorder is a monogenetic developmental and epileptic encephalopathy that affect the central nervous system. The broad phenotype includes global developmental delay, intellectual disability, epilepsy, musculoskeletal anomalies, altered pain perception, ataxia, hypotonia, nystagmus, and cerebellar atrophy.

References

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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  14. Quallo T, Alkhatib O, Gentry C, Andersson DA, Bevan S (August 2017). "G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons". eLife. 6. doi:10.7554/eLife.26138. PMC   5593501 . PMID   28826490.
  15. Behrendt M, Gruss F, Enzeroth R, Dembla S, Zhao S, Crassous PA, et al. (November 2020). "The structural basis for an on-off switch controlling Gβγ-mediated inhibition of TRPM3 channels". Proceedings of the National Academy of Sciences of the United States of America. 117 (46): 29090–29100. Bibcode:2020PNAS..11729090B. doi: 10.1073/pnas.2001177117 . PMC   7682392 . PMID   33122432.
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  25. Hossain Saad Md Zubayer, Xiang Liuruimin, Liao Yan-Shin, Reznikov Leah R., Du Jianyang (2021). "The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons". Frontiers in Pharmacology. 12:632711: 632711. doi: 10.3389/fphar.2021.632711 . PMC   7884864 . PMID   33603674.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading

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