MCOLN3

Summary

Gene Symbol: MCOLN3
Description: mucolipin 3
Alias: TRP-ML3, TRPML3, mucolipin-3, transient receptor potential channel mucolipin 3
Species: human
Products:     MCOLN3

Top Publications

  1. Kim H, Li Q, Tjon Kon Sang S, So I, Kiselyov K, Soyombo A, et al. A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype. EMBO J. 2008;27:1197-205 pubmed publisher
    b>TRPML3 belongs to the TRPML subfamily of the transient receptor potential (TRP) channels. The A419P mutation in TRPML3 causes the varitint-waddler phenotype as a result of gain-of-function mutation (GOF)...
  2. Di Palma F, Belyantseva I, Kim H, Vogt T, Kachar B, Noben Trauth K. Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice. Proc Natl Acad Sci U S A. 2002;99:14994-9 pubmed
    ..using a positional cloning strategy, we identify two additional members of the mucolipin gene family (Mcoln2 and Mcoln3) in the 350-kb Va(J) minimal interval and provide evidence for Mcoln3 as the gene mutated in varitint-waddler...
  3. Venkatachalam K, Hofmann T, Montell C. Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1. J Biol Chem. 2006;281:17517-27 pubmed
    ..Mammals encode two additional TRPML proteins named TRPML2 and TRPML3. Information regarding the propensity of these proteins to multimerize, their subcellular distribution and ..
  4. Nagata K, Zheng L, Madathany T, Castiglioni A, Bartles J, Garcia Anoveros J. The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration. Proc Natl Acad Sci U S A. 2008;105:353-8 pubmed
    ..Va mutation results in an alanine-to-proline substitution at residue 419 (A419P) of the presumed ion channel TRPML3. Another allele, Va(J), has the A419P mutation in addition to an I362T mutation...
  5. Curcio Morelli C, Zhang P, Venugopal B, Charles F, Browning M, Cantiello H, et al. Functional multimerization of mucolipin channel proteins. J Cell Physiol. 2010;222:328-35 pubmed publisher
    ..Along with TRPML1, there are two other TRPML family members, mucolipin-2 (TRPML2) and mucolipin-3 (TRPML3)...
  6. Grimm C, Jörs S, Guo Z, Obukhov A, Heller S. Constitutive activity of TRPML2 and TRPML3 channels versus activation by low extracellular sodium and small molecules. J Biol Chem. 2012;287:22701-8 pubmed publisher
    The transient receptor potential channels TRPML2 and TRPML3 (MCOLN2 and MCOLN3) are nonselective cation channels. They are widely expressed in mammals...
  7. Zeevi D, Lev S, Frumkin A, Minke B, Bach G. Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy. J Cell Sci. 2010;123:3112-24 pubmed publisher
    ..neurodegenerative lysosomal storage disorder, mucolipidosis type IV (MLIV), whereas a gain-of-function mutation in TRPML3 is principally implicated in the hearing-impaired and abnormally pigmented varitint-waddler mouse...
  8. Kim H, Li Q, Tjon Kon Sang S, So I, Kiselyov K, Muallem S. Gain-of-function mutation in TRPML3 causes the mouse Varitint-Waddler phenotype. J Biol Chem. 2007;282:36138-42 pubmed
    b>TRPML3 is a member of the TRPML subfamily of the transient receptor potential cation channel superfamily...
  9. Kim H, Soyombo A, Tjon Kon Sang S, So I, Muallem S. The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy. Traffic. 2009;10:1157-67 pubmed publisher
    b>TRPML3 is an inward rectifying Ca(2+) channel that is regulated by extracytosolic H(+). Although gain-of-function mutation in TRPML3 causes the varitint-waddler phenotype, the role of TRPML3 in cellular physiology is not known...

More Information

Publications33

  1. Benini A, Bozzato A, Mantovanelli S, Calvarini L, Giacopuzzi E, Bresciani R, et al. Characterization and expression analysis of mcoln1.1 and mcoln1.2, the putative zebrafish co-orthologs of the gene responsible for human mucolipidosis type IV. Int J Dev Biol. 2013;57:85-93 pubmed publisher
    ..1, mcoln1.2, mcoln2, mcoln3.1 and mcoln3.2. We focused our efforts on the characterization of the two putative zebrafish MCOLN1 co-orthologs...
  2. Feng X, Huang Y, Lu Y, Xiong J, Wong C, Yang P, et al. Drosophila TRPML forms PI(3,5)P2-activated cation channels in both endolysosomes and plasma membrane. J Biol Chem. 2014;289:4262-72 pubmed publisher
    ..Using TRPML A487P, which mimics the varitint-waddler (Va) mutant of mouse TRPML3 with constitutive whole-cell currents, we show that TRPML is biphasically regulated by extracytosolic pH, with an ..
  3. Krogsaeter E, Biel M, Wahl Schott C, Grimm C. The protein interaction networks of mucolipins and two-pore channels. Biochim Biophys Acta Mol Cell Res. 2019;1866:1111-1123 pubmed publisher
    ..Briefly, established TPC/TRPML functions and interaction partners ('interactomes') are discussed. Novel TRPML3 interactors are shown, and a meta-analysis of experimentally obtained channel interactomes conducted...
  4. Flores E, García Añoveros J. TRPML2 and the evolution of mucolipins. Adv Exp Med Biol. 2011;704:221-8 pubmed publisher
    ..and invertebrate chordates have only one Trpml gene, that Trpml1 and Trpml2 are common to vertebrates, and that Trpml3 is only found in tetrapods...
  5. García Añoveros J, Wiwatpanit T. TRPML2 and mucolipin evolution. Handb Exp Pharmacol. 2014;222:647-58 pubmed publisher
    ..The Mcoln2 gene is closely downstream from and in the same orientation as Mcoln3 in the genomes of most jawed vertebrates (from humans to sharks) with the exception of pigs, Xenopus tropicalis, ..
  6. Feng X, Xiong J, Lu Y, Xia X, Zhu M. Differential mechanisms of action of the mucolipin synthetic agonist, ML-SA1, on insect TRPML and mammalian TRPML1. Cell Calcium. 2014;56:446-56 pubmed publisher
    ..other hand, constitutive activation of TRPML by a mutation that mimics the varitint-waddler (Va) mutation of mouse TRPML3 rendered the insect channel sensitive to activation by ML-SA1 alone...
  7. Venkatachalam K, Wong C, Zhu M. The role of TRPMLs in endolysosomal trafficking and function. Cell Calcium. 2015;58:48-56 pubmed publisher
    ..storage disease, Mucolipidosis type IV, most mammals also express two other TRPML isoforms called TRPML2 and TRPML3. All three mammalian TRPMLs as well as TRPML related genes in other species including Caenorhabditis elegans and ..
  8. REMIS N, Wiwatpanit T, Castiglioni A, Flores E, Cantú J, García Añoveros J. Mucolipin co-deficiency causes accelerated endolysosomal vacuolation of enterocytes and failure-to-thrive from birth to weaning. PLoS Genet. 2014;10:e1004833 pubmed publisher
    ..before weaning express high levels of two endolysosomal cation channels, mucolipins 3 and 1 -products of Trpml3 and Trpml1 genes; moreover neonatal enterocytes of mice lacking both mucolipins (Trpml3-/-;Trpml1-/-) vacuolated ..
  9. Cuajungco M, Silva J, Habibi A, Valadez J. The mucolipin-2 (TRPML2) ion channel: a tissue-specific protein crucial to normal cell function. Pflugers Arch. 2016;468:177-92 pubmed publisher
    ..The TRPML protein subfamily consists of three members, TRPML1, TRPML2, and TRPML3, which are encoded by MCOLN1, MCOLN2, and MCOLN3 genes, respectively...
  10. Sun L, Hua Y, Vergarajauregui S, Diab H, Puertollano R. Novel Role of TRPML2 in the Regulation of the Innate Immune Response. J Immunol. 2015;195:4922-32 pubmed publisher
    ..In mammals, the TRPML family includes three members: TRPML1-3. Although TRPML1 and TRPML3 have been well characterized, the cellular function of TRPML2 has remained elusive...
  11. Tabur S, Oztuzcu S, Duzen I, Eraydın A, Eroglu S, Ozkaya M, et al. Role of the transient receptor potential (TRP) channel gene expressions and TRP melastatin (TRPM) channel gene polymorphisms in obesity-related metabolic syndrome. Eur Rev Med Pharmacol Sci. 2015;19:1388-97 pubmed
    ..Although there were marked decreases in TRPC1, TRPC3, TRPM2, TRPM5, TRPV4, TRPV5, TRPV6, MCOLN2 (TRPML2), and MCOLN3 (TRPML3) gene expressions, an augmentation was noted in TRPC6 gene expression...
  12. Miao Y, Li G, Zhang X, Xu H, Abraham S. A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion. Cell. 2015;161:1306-19 pubmed publisher
    ..This change is detected by mucolipin TRP channel 3 (TRPML3), a transient receptor potential cation channel localized to lysosomes...
  13. Wu X, Indzhykulian A, Niksch P, Webber R, Garcia Gonzalez M, Watnick T, et al. Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice. PLoS ONE. 2016;11:e0155577 pubmed publisher
    ..Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates...
  14. Fares H, Greenwald I. Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog. Nat Genet. 2001;28:64-8 pubmed
    ..elegans cup-5 mutant may be a useful model for studying conserved aspects of mucolipin-1 structure and function and for assessing the effects of potential therapeutic compounds...
  15. Hirschi M, Herzik M, Wie J, Suo Y, Borschel W, Ren D, et al. Cryo-electron microscopy structure of the lysosomal calcium-permeable channel TRPML3. Nature. 2017;550:411-414 pubmed publisher
    ..potential mucolipin (TRPML) channel family belongs to the TRP superfamily and is composed of three members: TRPML1-TRPML3. TRPMLs are the major Ca2+-permeable channels on late endosomes and lysosomes (LEL)...
  16. Düzen I, Yavuz F, Vuruşkan E, Saraçoğlu E, Poyraz F, Goksuluk H, et al. Leukocyte TRP channel gene expressions in patients with non-valvular atrial fibrillation. Sci Rep. 2017;7:9272 pubmed publisher
    ..We observed marked increases in MCOLN1 (TRPML1), MCOLN2 (TRPML2), MCOLN3 (TRPML3), TRPA1, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, ..
  17. Chen C, Butz E, Chao Y, Grishchuk Y, Becker L, Heller S, et al. Small Molecules for Early Endosome-Specific Patch Clamping. Cell Chem Biol. 2017;24:907-916.e4 pubmed publisher
    ..We apply this approach here to measure currents mediated by TRPML channels, in particular TRPML3, which we found to be functionally active in both EE and LE/LY in overexpressing cells as well as in endogenously ..
  18. Di Paola S, Scotto Rosato A, Medina D. TRPML1: The Ca(2+)retaker of the lysosome. Cell Calcium. 2018;69:112-121 pubmed publisher
    ..TRPML1 is the most extensively studied member of a small family of genes that also includes TRPML2 and TRPML3, and it has been found to participate in vesicular trafficking, lipid and ion homeostasis, and autophagy...
  19. Grimm C, Jörs S, Heller S. Life and death of sensory hair cells expressing constitutively active TRPML3. J Biol Chem. 2009;284:13823-31 pubmed publisher
    The varitint-waddler mutation A419P renders TRPML3 constitutively active, resulting in cationic overload, particularly in sustained influx of Ca(2+)...
  20. Choi S, Kim H. The Ca2+ channel TRPML3 specifically interacts with the mammalian ATG8 homologue GATE16 to regulate autophagy. Biochem Biophys Res Commun. 2014;443:56-61 pubmed publisher
    b>TRPML3 is a Ca(2+) permeable cation channel expressed in multiple intracellular compartments. Although TRPML3 is implicated in autophagy, how TRPML3 can regulate autophagy is not understood...
  21. Martina J, Lelouvier B, Puertollano R. The calcium channel mucolipin-3 is a novel regulator of trafficking along the endosomal pathway. Traffic. 2009;10:1143-56 pubmed publisher
    The varitint-waddler phenotype in mice is caused by gain-of-function mutations in mucolipin-3 (MCOLN3), a member of the mucolipin family of ion channels...
  22. Kim H, Yamaguchi S, Li Q, So I, Muallem S. Properties of the TRPML3 channel pore and its stable expansion by the Varitint-Waddler-causing mutation. J Biol Chem. 2010;285:16513-20 pubmed publisher
    b>TRPML3 is a H(+)-regulated Ca(2+) channel that shuttles between intracellular compartments and the plasma membrane. The A419P mutation causes the varitint-waddler phenotype as a result of gain-of-function (GOF)...
  23. Guo Z, Grimm C, Becker L, Ricci A, Heller S. A novel ion channel formed by interaction of TRPML3 with TRPV5. PLoS ONE. 2013;8:e58174 pubmed publisher
    b>TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels...
  24. Zhou X, Li M, Su D, Jia Q, Li H, Li X, et al. Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states. Nat Struct Mol Biol. 2017;: pubmed publisher
    b>TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH...