9b2a

Structural highlights

Function

TRPM3_MOUSE Constitutively active, non-selective divalent cation-conducting channel that is permeable to Ca(2+), Mn(2+), and Mg(2+), with a high permeability for Ca(2+) (PubMed:15824111, PubMed:20401728, PubMed:32780479). However, can be enhanced by increasing temperature and by ligands, including the endogenous neurosteroid pregnenolone sulfate and sphingosine-1 and suppressed by intracellular Mg(2+) (PubMed:20401728, PubMed:21555074). Implicated in a variety of cellular processes, including insulin/peptide secretion, vascular constriction and dilation, noxious heat sensing, inflammatory and spontaneous pain sensitivity (PubMed:21555074, PubMed:30853321, PubMed:33478988). In neurons of the dorsal root ganglia, functions as thermosensitive channel for the detection of noxious heat and spontaneous pain (PubMed:21555074, PubMed:33478988). Suggested to function as an ionotropic steroid receptor in beta-cell, indeed pregnenolone sulfate leads to Ca(2+) influx and enhanced insulin secretion (PubMed:18978782). Mediates Zn(2+) uptake into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion (PubMed:20401728). Forms heteromultimeric ion channels with TRPM1 which are permeable for Ca(2+) and Zn(2+) ions (By similarity). Exists as multiple splice variants which differ significantly in their biophysical properties (PubMed:15824111, PubMed:22961981).[UniProtKB:Q9HCF6]^{[1] [2] [3] [4] [5] [6] [7] [8]} Displays strongly reduced permeability for divalent cations and high selectivity toward monovalent cations.^[9] No channel activity.^[10] No channel activity.^[11]

References

1. ↑ Oberwinkler J, Lis A, Giehl KM, Flockerzi V, Philipp SE. Alternative splicing switches the divalent cation selectivity of TRPM3 channels. J Biol Chem. 2005 Jun 10;280(23):22540-8. PMID:15824111 doi:10.1074/jbc.M503092200
2. ↑ Wagner TF, Loch S, Lambert S, Straub I, Mannebach S, Mathar I, Düfer M, Lis A, Flockerzi V, Philipp SE, Oberwinkler J. Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells. Nat Cell Biol. 2008 Dec;10(12):1421-30. PMID:18978782 doi:10.1038/ncb1801
3. ↑ Wagner TF, Drews A, Loch S, Mohr F, Philipp SE, Lambert S, Oberwinkler J. TRPM3 channels provide a regulated influx pathway for zinc in pancreatic beta cells. Pflugers Arch. 2010 Sep;460(4):755-65. PMID:20401728 doi:10.1007/s00424-010-0838-9
4. ↑ Vriens J, Owsianik G, Hofmann T, Philipp SE, Stab J, Chen X, Benoit M, Xue F, Janssens A, Kerselaers S, Oberwinkler J, Vennekens R, Gudermann T, Nilius B, Voets T. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron. 2011 May 12;70(3):482-94. PMID:21555074 doi:10.1016/j.neuron.2011.02.051
5. ↑ Frühwald J, Camacho Londoño J, Dembla S, Mannebach S, Lis A, Drews A, Wissenbach U, Oberwinkler J, Philipp SE. Alternative splicing of a protein domain indispensable for function of transient receptor potential melastatin 3 (TRPM3) ion channels. J Biol Chem. 2012 Oct 26;287(44):36663-72. PMID:22961981 doi:10.1074/jbc.M112.396663
6. ↑ Alonso-Carbajo L, Alpizar YA, Startek JB, López-López JR, Pérez-García MT, Talavera K. Activation of the cation channel TRPM3 in perivascular nerves induces vasodilation of resistance arteries. J Mol Cell Cardiol. 2019 Apr;129:219-230. PMID:30853321 doi:10.1016/j.yjmcc.2019.03.003
7. ↑ Held K, Aloi VD, Freitas ACN, Janssens A, Segal A, Przibilla J, Philipp SE, Wang YT, Voets T, Vriens J. Pharmacological properties of TRPM3 isoforms are determined by the length of the pore loop. Br J Pharmacol. 2022 Jul;179(14):3560-3575. PMID:32780479 doi:10.1111/bph.15223
8. ↑ Su S, Yudin Y, Kim N, Tao YX, Rohacs T. TRPM3 Channels Play Roles in Heat Hypersensitivity and Spontaneous Pain after Nerve Injury. J Neurosci. 2021 Mar 17;41(11):2457-2474. PMID:33478988 doi:10.1523/JNEUROSCI.1551-20.2020
9. ↑ Oberwinkler J, Lis A, Giehl KM, Flockerzi V, Philipp SE. Alternative splicing switches the divalent cation selectivity of TRPM3 channels. J Biol Chem. 2005 Jun 10;280(23):22540-8. PMID:15824111 doi:10.1074/jbc.M503092200
10. ↑ Frühwald J, Camacho Londoño J, Dembla S, Mannebach S, Lis A, Drews A, Wissenbach U, Oberwinkler J, Philipp SE. Alternative splicing of a protein domain indispensable for function of transient receptor potential melastatin 3 (TRPM3) ion channels. J Biol Chem. 2012 Oct 26;287(44):36663-72. PMID:22961981 doi:10.1074/jbc.M112.396663
11. ↑ Frühwald J, Camacho Londoño J, Dembla S, Mannebach S, Lis A, Drews A, Wissenbach U, Oberwinkler J, Philipp SE. Alternative splicing of a protein domain indispensable for function of transient receptor potential melastatin 3 (TRPM3) ion channels. J Biol Chem. 2012 Oct 26;287(44):36663-72. PMID:22961981 doi:10.1074/jbc.M112.396663