全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS Genetics  2013 

Basolateral Mg2+ Extrusion via CNNM4 Mediates Transcellular Mg2+ Transport across Epithelia: A Mouse Model

DOI: 10.1371/journal.pgen.1003983

Full-Text   Cite this paper   Add to My Lib

Abstract:

Transcellular Mg2+ transport across epithelia, involving both apical entry and basolateral extrusion, is essential for magnesium homeostasis, but molecules involved in basolateral extrusion have not yet been identified. Here, we show that CNNM4 is the basolaterally located Mg2+ extrusion molecule. CNNM4 is strongly expressed in intestinal epithelia and localizes to their basolateral membrane. CNNM4-knockout mice showed hypomagnesemia due to the intestinal malabsorption of magnesium, suggesting its role in Mg2+ extrusion to the inner parts of body. Imaging analyses revealed that CNNM4 can extrude Mg2+ by exchanging intracellular Mg2+ with extracellular Na+. Furthermore, CNNM4 mutations cause Jalili syndrome, characterized by recessive amelogenesis imperfecta with cone-rod dystrophy. CNNM4-knockout mice showed defective amelogenesis, and CNNM4 again localizes to the basolateral membrane of ameloblasts, the enamel-forming epithelial cells. Missense point mutations associated with the disease abolish the Mg2+ extrusion activity. These results demonstrate the crucial importance of Mg2+ extrusion by CNNM4 in organismal and topical regulation of magnesium.

References

[1]  Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, et al. (1999) Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 285: 103–106. doi: 10.1126/science.285.5424.103
[2]  Konrad M, Schaller A, Seelow D, Pandey AV, Waldegger S, et al. (2006) Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement. Am J Hum Genet 79: 949–957. doi: 10.1086/508617
[3]  Hou J, Paul DL, Goodenough DA (2005) Paracellin-1 and the modulation of ion selectivity of tight junctions. J Cell Sci 118: 5109–5118. doi: 10.1242/jcs.02631
[4]  Schlingmann KP, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, et al. (2002) Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 31: 166–170. doi: 10.1038/ng889
[5]  Walder RY, Landau D, Meyer P, Shalev H, Tsolia M, et al. (2002) Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet 31: 171–174. doi: 10.1038/ng901
[6]  Voets T, Nilius B, Hoefs S, van der Kemp AW, Droogmans G, et al. (2004) TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem 279: 19–25. doi: 10.1074/jbc.m311201200
[7]  Ryazanova LV, Rondon LJ, Zierler S, Hu Z, Galli J, et al. (2010) TRPM7 is essential for Mg(2+) homeostasis in mammals. Nat Commun 1: 109. doi: 10.1038/ncomms1108
[8]  Teramoto T, Lambie EJ, Iwasaki K (2005) Differential regulation of TRPM channels governs electrolyte homeostasis in the C. elegans intestine. Cell Metab 1: 343–354. doi: 10.1016/j.cmet.2005.04.007
[9]  Teramoto T, Sternick LA, Kage-Nakadai E, Sajjadi S, Siembida J, et al. (2010) Magnesium excretion in C. elegans requires the activity of the GTL-2 TRPM channel. PLoS One 5: e9589. doi: 10.1371/journal.pone.0009589
[10]  Wang CY, Shi JD, Yang P, Kumar PG, Li QZ, et al. (2003) Molecular cloning and characterization of a novel gene family of four ancient conserved domain proteins (ACDP). Gene 306: 37–44. doi: 10.1016/s0378-1119(02)01210-6
[11]  Meyer TE, Verwoert GC, Hwang SJ, Glazer NL, Smith AV, et al. (2010) Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels. PLoS Genet 6: e1001045. doi: 10.1371/journal.pgen.1001045
[12]  Stuiver M, Lainez S, Will C, Terryn S, Günzel D, et al. (2011) CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia. Am J Hum Genet 88: 333–343. doi: 10.1016/j.ajhg.2011.02.005
[13]  Gibson MM, Bagga DA, Miller CG, Maguire ME (1991) Magnesium transport in Salmonella typhimurium: the influence of new mutations conferring Co2+ resistance on the CorA Mg2+ transport system. Mol Microbiol 5: 2753–2762. doi: 10.1111/j.1365-2958.1991.tb01984.x
[14]  Goytain A, Quamme GA (2005) Functional characterization of ACDP2 (ancient conserved domain protein), a divalent metal transporter. Physiol Genomics 22: 382–389. doi: 10.1152/physiolgenomics.00058.2005
[15]  Sponder G, Svidova S, Schweigel M, Vormann J, Kolisek M (2010) Splice-variant 1 of the ancient domain protein 2 (ACDP2) complements the magnesium-deficient growth phenotype of Salmonella enterica sv. typhimurium strain MM281. Magnes Res 23: 105–114.
[16]  Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, et al. (2009) Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet 84: 266–273. doi: 10.1016/j.ajhg.2009.01.009
[17]  Polok B, Escher P, Ambresin A, Chouery E, Bolay S, et al. (2009) Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta. Am J Hum Genet 84: 259–265. doi: 10.1016/j.ajhg.2009.01.006
[18]  de Baaij JH, Stuiver M, Meij IC, Lainez S, Kopplin K, et al. (2012) Membrane topology and intracellular processing of cyclin M2 (CNNM2). J Biol Chem 287: 13644–13655. doi: 10.1074/jbc.m112.342204
[19]  Casaletto JB, Saotome I, Curto M, McClatchey AI (2011) Ezrin-mediated apical integrity is required for intestinal homeostasis. Proc Natl Acad Sci USA 108: 11924–11929. doi: 10.1073/pnas.1103418108
[20]  Su L, Shen L, Clayburgh DR, Nalle SC, Sullivan EA, et al. (2009) Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology 136: 551–563. doi: 10.1053/j.gastro.2008.10.081
[21]  Kucharski LM, Lubbe WJ, Maguire ME (2000) Cation hexaammines are selective and potent inhibitors of the CorA magnesium transport system. J Biol Chem 275: 16767–16773. doi: 10.1074/jbc.m001507200
[22]  Kolisek M, Launay P, Beck A, Sponder G, Serafini N, et al. (2008) SLC41A1 is a novel mammalian Mg2+ carrier. J Biol Chem 283: 16235–16247. doi: 10.1074/jbc.m707276200
[23]  Smith CE (1998) Cellular and chemical events during enamel maturation. Crit Rev Oral Biol Med 9: 128–161. doi: 10.1177/10454411980090020101
[24]  Inai T, Sengoku A, Hirose E, Iida H, Shibata Y (2008) Differential expression of the tight junction proteins, claudin-1, claudin-4, occludin, ZO-1, and PAR3, in the ameloblasts of rat upper incisors. Anat Rec 291: 577–585. doi: 10.1002/ar.20683
[25]  Meindl A, Dry K, Herrmann K, Manson F, Ciccodicola A, et al. (1996) A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nat Genet 13: 35–42. doi: 10.1038/ng0596-35
[26]  Hong DH, Pawlyk BS, Shang J, Sandberg MA, Berson EL, et al. (2000) A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proc Natl Acad Sci USA 97: 3649–3654. doi: 10.1073/pnas.97.7.3649
[27]  Günther T (2006) Mechanisms, regulation and pathologic significance of Mg2+ efflux from erythrocytes. Magnes Res 19: 190–198.
[28]  Günther T (2007) Na+/Mg2+ antiport in non-erythrocyte vertebrate cells. Magnes Res 20: 89–99.
[29]  Kolisek M, Nestler A, Vormann J, Schweigel-R?ntgen M (2012) Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger. Am J Physiol Cell Physiol 302: C318–326. doi: 10.1152/ajpcell.00289.2011
[30]  Wabakken T, Rian E, Kveine M, Aasheim HC (2003) The human solute carrier SLC41A1 belongs to a novel eukaryotic subfamily with homology to prokaryotic MgtE Mg2+ transporters. Biochem Biophys Res Commun 306: 718–724. doi: 10.1016/s0006-291x(03)01030-1
[31]  Hurd TW, Otto EA, Mishima E, Gee HY, Inoue H, et al. (2013) Mutation of the Mg2+ transporter SLC41A1 results in a nephronophthisis-like phenotype. J Am Soc Nephrol 24: 967–977. doi: 10.1681/asn.2012101034
[32]  Navarro-González JF, Mora-Fernández C, García-Pérez J (2009) Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial 22: 37–44. doi: 10.1111/j.1525-139x.2008.00530.x
[33]  Konrad M, Schlingmann KP, Gudermann T (2004) Insights into the molecular nature of magnesium homeostasis. Am J Physiol Renal Physiol 286: F599–605.
[34]  Dimke H, Hoenderop JG, Bindels RJ (2011) Molecular basis of epithelial Ca2+ and Mg2+ transport: insights from the TRP channel family. J Physiol 589: 1535–1542. doi: 10.1113/jphysiol.2010.199869
[35]  J?levik B, Odelius H, Dietz W, Norén J (2001) Secondary ion mass spectrometry and X-ray microanalysis of hypomineralized enamel in human permanent first molars. Arch Oral Biol 46: 239–247. doi: 10.1016/s0003-9969(00)00113-8
[36]  Itoh M, Yonemura S, Nagafuchi A, Tsukita S, Tsukita S (1991) 220-kD undercoat-constitutive protein: its specific localization at cadherin-based cell-cell adhesion sites. J Cell Biol 115: 1449–1462. doi: 10.1083/jcb.115.5.1449
[37]  Koike C, Obara T, Uriu Y, Numata T, Sanuki R, et al. (2010) TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proc Natl Acad Sci USA 107: 332–337. doi: 10.1073/pnas.0912730107
[38]  Omori Y, Chaya T, Katoh K, Kajimura N, Sato S, et al. (2010) Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival. Proc Natl Acad Sci USA 107: 22671–22676. doi: 10.1073/pnas.1009437108
[39]  Sato S, Omori Y, Katoh K, Kondo M, Kanagawa M, et al. (2008) Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation. Nat Neurosci 11: 923–931. doi: 10.1038/nn.2160
[40]  Fujita T, Hirooka K, Nakamura T, Itano T, Nishiyama A, et al. (2012) Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels. Invest Ophthalmol Vis Sci 53: 4099–4110. doi: 10.1167/iovs.11-9167
[41]  Hibino H, Kurachi Y (2007) Distinct detergent-resistant membrane microdomains (lipid rafts) respectively harvest K(+) and water transport systems in brain astroglia. Eur J Neurosci 26: 2539–2555. doi: 10.1111/j.1460-9568.2007.05876.x
[42]  Günther T (2006) Concentration, compartmentation and metabolic function of intracellular free Mg2+. Magnes Res 19: 225–236.
[43]  Schilling T, Eder C (2004) A novel physiological mechanism of glycine-induced immunomodulation: Na+-coupled amino acid transporter currents in cultured brain macrophages. J Physiol 559: 35–40. doi: 10.1113/jphysiol.2004.070763
[44]  Leone FA, Baranauskas JA, Furriel RP, Borin IA (2005) SigrafW: An easy-to-use program for fitting enzyme kinetic data. Biochem Mol Biol Educ 33: 399–403. doi: 10.1002/bmb.2005.49403306399
[45]  Tsuda T, Nemoto N, Kawakami K, Mochizuki E, Kishida S, et al. (2011) SEM observation of wet biological specimens pretreated with room-temperature ionic liquid. Chembiochem 12: 2547–2550. doi: 10.1002/cbic.201100476

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133