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Alternative Splicing Regulates the Subcellular Localization of Divalent Metal Transporter 1 Isoforms
Open accessAbstract
Divalent metal transporter 1 (DMT1) is responsible for dietary-iron absorption from apical plasma membrane in the duodenum and iron acquisition from the transferrin cycle endosomes in peripheral tissues. Two isoforms of the DMT1 transcript generated by alternative splicing of the 3′ exons have been identified in mouse, rat, and human. These isoforms can be distinguished by the different C-terminal amino acid sequences and by the presence (DMT1A) or absence (DMT1B) of an iron response element located in the 3′ untranslated region of the mRNA. However, it has been still unknown whether the structural differences between the two DMT1 isoforms is functionally important. Here, we report that each DMT1 isoform exhibits a differential cell type–specific expression patterns and distinct subcellular localizations. DMT1A is predominantly expressed by epithelial cell lines, whereas DMT1B is expressed by the blood cell lines. In HEp-2 cells, GFP-tagged DMT1A is localized in late endosomes and lysosomes, whereas GFP-tagged DMT1B is localized in early endosomes. Using site-directed mutagenesis, a Y 555 XLXX sequence in the cytoplasmic tail of DMT1B has been identified as an important signal sequence for the early endosomal-targeting of DMT1B. In polarized MDCK cells, GFP-tagged DMT1A and DMT1B are localized in the apical plasma membrane and their respective specific endosomes. Disruption of the N-glycosylation sites in each of the DMT1 isoforms affects their polarized distribution into the apical plasma membrane but not their correct endosomal localization. Our data indicate that the cell type–specific expression patterns and the distinct subcellular localizations of two DMT1 isoforms may be involved in the different iron acquisition steps from the subcellular membranes in various cell types.
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“These mice also demonstrated an increase in markers of oxidative stress, including SOD activity, oxidative protein modifications, and apoptotic indicators (291).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [291]
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“Furthermore, generation of heterozygous ferritin H–null mutants shows brain iron levels similar to those of the wild type, despite a 50% expression of ferritin H that corresponded with increases in proteins involved in iron regulation, such as Tf, TfR, ferritin L, DMT1, and Cp (291).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [291]
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“Furthermore, generation of heterozygous ferritin H–null mutants shows brain iron levels similar to those of the wild type, despite a 50% expression of ferritin H that corresponded with increases in proteins involved in iron regulation, such as Tf, TfR, ferritin L, DMT1, and Cp (291).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [291]
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Catch me if you can! Novel aspects of cadmium transport in mammalian cells
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Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1)
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Iron export through the transporter ferroportin 1 is modulated by the iron chaperone PCBP2
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“Then, the postmitochondrial fraction was centrifuged at 100,000 g for 30 min at 4 °C to obtain the membrane fraction as described previously (14, 17).”
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BackgroundMethodResultInfluentialSelf-citationIron homeostasis and organismal aging
Zeidan, R. S., Han, S. M., Leeuwenburgh, C., & Xiao, R. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101510 · Cited by 155
The iron transporter ferroportin can also function as a manganese exporter
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“Alternative splicing produces Nramp2 isoforms (Gruenheid et al. 1995; Fleming et al. 1997; Lee et al. 1998; Tabuchi et al. 2002); Nramp2 isoform I is found predominantly at the apical membrane of epithelial cells (duodenum, kidney) (Canonne-Hergaux et al.”
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“Two forms of Pcyt2 may be important for numerous reasons in addition to moderating catalytic activity, including protein–protein interactions and specific cellular localizations (Kogo and Fujimoto 2000; Kogo et al. 2002; Tabuchi et al. 2002).”
BackgroundDcytb (Cybrd1) functions as both a ferric and a cupric reductase in vitro
Wyman, S., Simpson, R. J., McKie, A. T., & Sharp, P. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.05.010 · Cited by 125
“Endogenous DMT1 protein was detected using rabbit anti-DMT1 (NRAMP24-A) antibody (Alpha Diagnostics Inc., San Antonio, Texas, USA).”
MethodInfluentialMims, M. P., & Prchal, J. T. (2005) · Hematology · doi:10.1080/10245330500093419 · Cited by 123
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BackgroundSLC11 family of H + -coupled metal-ion transporters NRAMP1 and DMT1
Mackenzie, B., & Hediger, M. A. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1141-9 · Cited by 127
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Iron Regulation and the Cell Cycle
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“It is expressed as four different isoforms as a result of differential transcription initiation and splicing at two alternative 30 ends (Tabuchi et al. 2002; Mackenzie et al. 2007).”
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Iron transport in the kidney: implications for physiology and cadmium nephrotoxicity
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ACBD2/ECI2-Mediated Peroxisome-Mitochondria Interactions in Leydig Cell Steroid Biosynthesis
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H+-Coupled Divalent Metal-Ion Transporter-1
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“In addition, variable 3’-end mRNA processing yields two transcripts that differ in their 3’-translated and untranslated regions (UTRs).(3,6) One transcript contains an ironresponsive element (+IRE) in its 3’-UTR, which can alter the mRNA stability according to iron status.”
BackgroundInfluentialA general map of iron metabolism and tissue-specific subnetworks
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“In the larynx carcinoma cell line HEp-2 and polarized MadinDarby canine kidney (MDCK-II) cells, green fluorescent protein (GFP)-tagged DMT1 IRE localized to late endosomes and lysosomes, whereas GFP-tagged DMT1 IRE was found to localize to subapical early endosomes, but not plasma membranes (27).”
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“The localizations of the DMT1B-I and DMT1B-II isoforms were previously reported [40] (data not shown).”
BackgroundSelf-citationFOXP3 ensembles in T‐cell regulation
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“The cause for this selectivity is not known but may possibly involve differences in the distribution of the different isoforms of DMT1 in separate and distinct endosomal vesicles which are sorted and modified independently within cells (Tabuchi et al. 2002; Touret et al. 2003; Lis et al. 2004).”
BackgroundGenome-wide RNAi Screen Identifies SEC61A and VCP as Conserved Regulators of Sindbis Virus Entry
Panda, D., Rose, P. P., Hanna, S. L., Gold, B., Hopkins, K. C., Lyde, R. B., Marks, M. S., & Cherry, S. R. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.11.028 · Cited by 75
“SEC61A and VCP regulate NRAMP2 localization Previous studies have shown that NRAMP2 rapidly shuttles between endosomal compartments and the plasma membrane (Lam-Yuk-Tseung and Gros, 2006; Tabuchi et al., 2002).”
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“Another isoform with an IRE domain in its 3 region (DMT1B-I) is localized in the late endosome/lysosome to retrieve iron released during lysosomal catabolism of iron-containing proteins (16, 17).”
BackgroundSelf-citationPhysiology and Pathology of Endosome‐to‐Golgi Retrograde Sorting
Burd, C. G. (2011) · Traffic · doi:10.1111/j.1600-0854.2011.01188.x · Cited by 75
“Alternative splicing of DMT1 pre-mRNA generates two forms of DMT that localize to distinct endosomal compartments (28).”
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DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration
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Self-citationMolecular physiology and pathophysiology of lysosomal membrane transporters
Sagné, C., & Gasnier, B. (2008) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-008-0879-9 · Cited by 55
“IRE + splicing isoform H + symport Gunshin et al (1997), Tabuchi et al (2002)”
BackgroundIron Imports. V. Transport of iron through the intestinal epithelium
Ma, Y., YEH, M. K. Y., Yeh, K., & Glass, J. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00489.2005 · Cited by 55
“In a variety of studies examining subcellular localization of transfected DMT1, the protein has been localized in intracellular vesicular compartments (4, 24).”
BackgroundSchaer, C. A., Vallelian, F., Imhof, A., Schoedon, G., & Schaer, D. J. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0407226 · Cited by 56
“Hb-Hp traffics through the HCP-1/DMT-1Bpositive endosomal compartment to DMT-1Apositive lysosomes We coexpressed CD163 with EGFP fusion constructs of the two major splice variants of DMT-1, which are targeted to early endosomes (DMT-1B) and late endosomes/lysosomes (DMT- 1A) [23].”
MethodInfluentialMutations in the Gene Encoding DMT1: Clinical Presentation and Treatment
Iolascon, A., & Falco, L. D. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.06.005 · Cited by 53
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“Further complexity is added by the post-translational glycosylation of DMT1, which produces two different glycosylated molecular components: the immature, partially glycosylated, endo H-sensitive form and the mature, fully glycosylated, PNGaseF-sensitive component, with molecular masses of 60 and 90 kDa, respectively…”
InfluentialGarrick, M. D. (2010) · Genes & Nutrition · doi:10.1007/s12263-010-0184-8 · Cited by 52
“Existing data do suggest the presence of such distinctions [5, 15, 24, 26, 38, 39, 48, 49].”
BackgroundLis, A., Paradkar, P. N., Singleton, S., Kuo, H.-C., Garrick, M. D., & Roth, J. A. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.03.023 · Cited by 49
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“In control tissue, none of the metal transporting proteins exhibited detectable surface membrane localization as has been seen for DMT1 and MTP1 in other metal transporting tissues (Abboud and Haile, 2000; Tabuchi et al., 2002; Yang et al., 2002).”
BackgroundMethodChong, W. S., Kwan, P. C., Chan, L. Y., Chiu, P., Cheung, T. K., & Lau, T. K. (2005) · Human Reproduction · doi:10.1093/humrep/dei246 · Cited by 48
“The proteins of DMT1-IRE and DMT1-nonIRE differ in their last C-terminal 18 or 25 amino acids and are found to have differential cell type specificity and distinct subcellular localization in the adult human (Canonne-Hergaux et al., 1999; Tabuchi et al., 2002; Tchernitchko et al., 2002).”
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“Detection of DMT1 by immunoblotting results in the visualization of several bands spanning a range from 30 to 100 kDa (Tabuchi et al. 2002) that appears to vary according to the tissue examined (Cheong et al.”
BackgroundFunctional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake
Priwitzerova, M., Nie, G., Sheftel, A. D., Pospı́šilová, D., Divoký, V., & Ponka, P. (2005) · Blood · doi:10.1182/blood-2005-04-1550 · Cited by 46
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“This suggests that DMT1 might be subjected to post-translation processing other than glycosylation, a prospect supported by the finding that exogenous over-expression of DMT1 in monkey kidney fibroblast (COS-7) cells lead to a deglycosylated form of 50 kDa (Tabuchi et al. 2002).”
BackgroundResultInfluentialNúñez, M. T., Tapia, V., Rojas, A., Aguirre, P., Gómez, F., & Nualart, F. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00168.2009 · Cited by 44
“In retrospective, the finding of DMT1 in the basolateral membrane of Caco-2 cells or in the basal domains of enterocytes is not surprising, since DMT1 is needed for iron transport out of the endocytic vesicle during basolateral transferrin endocytosis (42).”
BackgroundIron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction
Matsuoka, T., Abe, M., & Kobayashi, H. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073745 · Cited by 53
“…heme iron, typically in the form of ferric iron (Fe 3+ ), is reduced to ferrous iron (Fe 2+ by duodenal cytochrome B [29] and transported into enterocytes by divalent metal transporter 1 (DMT1) [30 – 32] Heme iron is broken down into Fe 2+ and biliverdin by heme oxygenases (HO)-1 and HO-2 [33–35].”
BackgroundEvolution of Differences in Transport Function in Slc11a Family Members
Techau, M. E., Valdez-Taubas, J., Popoff, J.-F., Francis, R., Seaman, M., & Blackwell, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707057200 · Cited by 42
Johnson, D., Yamaji, S., Tennant, J. P., Srai, S. K., & Sharp, P. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.02.035 · Cited by 41
Expression and localization of different forms of DMT1 in normal and tumor astroglial cells
Lis, A., Barone, T. A., Paradkar, P. N., Plunkett, R. J., & Roth, J. A. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2003.11.023 · Cited by 41
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Wang, X., Li, G. J., & Zheng, W. (2008) · Experimental Biology and Medicine · doi:10.3181/0803-rm-104 · Cited by 38
Role of NADPH oxidase in the regulation of autophagy in cardiomyocytes
Sciarretta, S., Yee, D., Ammann, P. B., Nagarajan, N., Volpe, M., Frati, G., & Sadoshima, J. (2014) · Clinical Science · doi:10.1042/cs20140336 · Cited by 36
Núñez, M. T. (2010) · BioFactors · doi:10.1002/biof.84 · Cited by 36
“The finding of DMT1 in the basolateral membrane of Caco-2 cells and in the basal domains of enterocytes comes to no surprise, since DMT1 is needed for iron transport out of the endocytic vesicle during basolateral transferrin endocytosis [75].”
BackgroundXu, M.-J., Saxena, N., Vrana, M., Zhang, H., Kumar, V., Billington, S., Khojasteh, C., Heyward, S., Unadkat, J., & Prasad, B. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b01913 · Cited by 34
Jamieson, S. E., White, J. K., Howson, J. M. M., Pask, R., Smith, A., Brayne, C., Evans, J. G., Xuereb, J. H., Cairns, N. J., Rubinsztein, D. C., et al. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.10.038 · Cited by 34
Ingrassia, R., Memo, M., & Garavaglia, B. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00018 · Cited by 33
Adaptive Changes Allow Targeting of Ferroptosis for Glioma Treatment
Huang, R., Dong, R., Wang, N., He, Y., Zhu, P., Wang, C., Lan, B., Gao, Y., & Sun, L. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01092-5 · Cited by 36
Gruper, Y., Bar, J., Bacharach, E., & Ehrlich, R. L. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20349 · Cited by 31
“The sub-cellular localization, mechanism of action, and the destination of iron transported by the two isoforms are not completely understood (Tabuchi et al., 2002) and it is becoming increasingly clear that the expression of the two variants is not mutually exclusive and that the IRE and non-IRE…”
BackgroundIle, K. E., Davis, W., Boyd, J. T., Soulika, A. M., & Tew, K. D. (2004) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/j.bbaexp.2004.01.007 · Cited by 31
White, J. K., Stewart, A., Popoff, J.-F., Wilson, S., & Blackwell, J. M. (2004) · Biochemical Journal · doi:10.1042/bj20040808 · Cited by 30
Isoform‐Specific Localization of the Deubiquitinase USP33 to the Golgi Apparatus
Thorne, C., Eccles, R. L., Coulson, J. M., Urbé, S., & Clague, M. J. (2011) · Traffic · doi:10.1111/j.1600-0854.2011.01261.x · Cited by 26
“Thus, we are able to add a first example of a USP family member to the inventory of proteins, for which alternative splicing can determine sub-cellular distribution (28,29).”
BackgroundOkazaki, Y., Ma, Y., YEH, M. K. Y., Yin, H., Li, Z., Yeh, K., & Glass, J. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00545.2010 · Cited by 26
“The isoforms appear to dictate tissue-specific expression patterns as well as distinct subcellular localizations (16, 27).”
BackgroundNatural history of SLC11 genes in vertebrates: tales from the fish world
Neves, J. V., Wilson, J. M., Kuhl, H., Reinhardt, R., Castro, L. F. C., & Rodrigues, P. N. (2011) · BMC Evolutionary Biology · doi:10.1186/1471-2148-11-106 · Cited by 24
“This observation provides further evidence for a sub-functionalization of slc11a2 homologs in sea bass, with slc11a2-a localization resembling that of the mammalian SLC11A2 IRE-positive isoforms and slc11a2-b with the more general distribution of mammalian SLC11A2 IRE-negative isoforms [62, 74 ,77].”
BackgroundCloning and characterization of the osteoarthritis-associated gene DVWA
Nakajima, M., Miyamoto, Y., & Ikegawa, S. (2010) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-010-0230-z · Cited by 24
“Some of the splice variants occur at the coding region, resulting in isoforms with different tissue and cellular localizations [22, 23].”
BackgroundAlvarado-Díaz, C. P., Núñez, M. T., Devoto, L., & González-Ramos, R. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.04.002 · Cited by 25
Genetically programmed superparamagnetic behavior of mammalian cells
Kim, T., Moore, D., & Fussenegger, M. (2012) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2012.09.019 · Cited by 24
Stewart, A. K., Kurschat, C. E., Vaughan‐Jones, R. D., Shmukler, B. E., & Alper, S. L. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.136119 · Cited by 22
“H+ cotransporter DMT1 prevents sorting to the apical membrane (Tabuchi et al. 2002).”
BackgroundYanatori, I., Richardson, D. R., Toyokuni, S., & Kishi, F. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108071 · Cited by 23
Self-citationLam-Yuk-Tseung, S., Picard, V., & Gros, P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601828200 · Cited by 21
Shirase, T., Mori, K., Okazaki, Y., Itoh, K., Yamamoto, M. P., Tabuchi, M., Kishi, F., Jiang, L., Akatsuka, S., Nakao, K., et al. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090823 · Cited by 22
Self-citationBalušíková, K., Neubauerová, J., Dostalikova‐Cimburova, M., Horák, J., & Kovár̆, J. (2008) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-008-9926-y · Cited by 20
“It was shown that the DMT1 IRE form is expressed predominantly by epithelial cell lines, whereas the non-IRE form is expressed by blood cell lines [46].”
BackgroundMycobacterium-InducibleNrampin Striped Bass (Morone saxatilis)
Burge, E. J., Gauthier, D. T., Ottinger, C. A., & Veld, P. A. V. (2004) · Infection and Immunity · doi:10.1128/iai.72.3.1626-1636.2004 · Cited by 21
“Alternative splicing has been identified in several Nramp2 homologs, including human (40), mouse and rat (56), macaque (65), and channel catfish (12) homologs.”
BackgroundEsparza, A., Gerdtzen, Z. P., Olivera‐Nappa, Á., Salgado, J. C., & Núñez, M. T. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00412.2014 · Cited by 20
Glycosylation of solute carriers: mechanisms and functional consequences
Borbye‐Lorenzen, N., Carlsson, M. C., & Pedersen, S. F. (2015) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-015-1730-4 · Cited by 21
“Some transporters do exhibit reduced activity when their N-glycans are removed [35, 120, 135]; others traffic to atypical compartments of polarized cell layers [63, 107], and in others, the N-glycans may serve a role as environmental sensors [6].”
BackgroundSanthakumar, S., Aaron, R., Cherian, A. G., Abraham, V. J., George, B., Lipiński, P., & Edison, E. S. (2023) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2023.102727 · Cited by 20
Cardiac iron metabolism during aging – Role of inflammation and proteolysis
Walter, S., Mertens, C., Muckenthaler, M. U., & Ott, C. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111869 · Cited by 19
“Thereby, four different isoforms can be synthesized, including -IRE 1A, +IRE 1A, -IRE 1B and +IRE 1B (Tabuchi et al., 2002; Garrick et al., 2012; Ingrassia et al., 2019).”
Kleist, T. J., & Luan, S. (2015) · Plant Cell & Environment · doi:10.1111/pce.12599 · Cited by 19
Mitosis-Coupled, Microtubule-Dependent Clustering of Endosomal Vesicles around Centrosomes
Takatsu, H., Katoh, Y., Ueda, T., Waguri, S., Murayama, T., Takahashi, S., Shin, H., & Nakayama, K. (2013) · Cell Structure and Function · doi:10.1247/csf.12028 · Cited by 18
“, 2002); DMT1-II is responsible for transport across endosomal membranes of iron internalized via the Tfn-TfnR complex (Tabuchi et al., 2002).”
BackgroundMethodInfluentialBury, N. R., Boyle, D., & Cooper, C. A. (2011) · Fish physiology · doi:10.1016/s1546-5098(11)31004-7 · Cited by 19
Homeostatic regulation of trace mineral transport by ubiquitination of membrane transporters
Hennigar, S. R., & McClung, J. P. (2015) · Nutrition Reviews · doi:10.1093/nutrit/nuv060 · Cited by 16
Yanatori, I., Yasui, Y., Noguchi, Y., & Kishi, F. (2014) · Cell Biology International · doi:10.1002/cbin.10403 · Cited by 18
“Ferristatin II reduces iron uptake across the plasma membrane DMT1 has four isoforms (Hubert andHentze, 2002; Tabuchi et al., 2000, 2002, 2010).”
BackgroundSelf-citationMehlferber, E. C., Benowitz, K. M., Roy-Zokan, E. M., McKinney, E. C., Cunningham, C. B., & Moore, A. J. (2017) · G3 Genes Genomes Genetics · doi:10.1534/g3.117.300183 · Cited by 16
“The intracellular localization motif, which in humans is composed of the amino acids located at positions 555 (D on Figure 1) and 557 (E on Figure 1) and has been implicated in the intracellular localization of Nramp2, marks the beginning of the alternative splice site.”
InfluentialContributions of Saccharomyces cerevisiae to Understanding Mammalian Gene Function and Therapy
Zhang, N., & Bilsland, E. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-173-4_28 · Cited by 17
Comparative Analysis of Two slc11 ( Nramp ) Loci in Takifugu rubripes
Sibthorpe, D., Baker, A.-M., Gilmartin, B. J., Blackwell, J. M., & White, J. K. (2004) · DNA and Cell Biology · doi:10.1089/104454904322745925 · Cited by 16
“What controls the differential targeting of two alternatively spliced isoforms of Slc11a2 encoding distinct C-termini and 3 9 UTR (Tabuchi et al ., 2002; JKW, unpublished data)?”
InfluentialKuo, H. C., Smith, J. J., Lis, A., Zhao, L., Gonsiorek, E. A., Zhou, X., Higgins, D. M., Roth, J. A., Garrick, M. D., & Garrick, L. M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20112 · Cited by 15
“…was 52 kD. Sizes reported in the literature vary considerably for DMT1 (Gruenheid et al., 1999; CanonneHergeaux et al., 2000; Yeh et al., 2000; Burdo et al., 2001; Ferguson et al., 2001; Tabuchi et al., 2002), but none of the prior studies used antibodies with specificity for exon 1A of DMT1.”
BackgroundThe solute carrier family 11 transporters: a bridge between iron homeostasis and tumor biology
Banerjee, R., Bintee, B., Manickasamy, M. K., Jha, S., Alqahtani, M. S., Abbas, M., Goel, A., Sethi, G., Ma, Z., & Kunnumakkara, A. B. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02293-x · Cited by 14
“Likewise, in SLC11A2, the 555 YLLNT 559 motif within the C-terminus of the isoform II is responsible for targeting the protein to transferrin (Tf)-positive early recycling endosomes [50, 55].”
The Roles of DMT1 in Inflammatory and Degenerative Diseases
Liu, H., Li, M., Deng, Y. X., Hou, Y., Hou, L., Zhang, X., Zheng, Z., Guo, F., & Sun, K. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04687-x · Cited by 14
Metadata
- Authors
- Tabuchi, M., Tanaka, N., Nishida-Kitayama, J., Ohno, H., & Kishi, F.
- Affiliations
- Yamaguchi University (JP)
- Kanazawa University (JP)
- Center for Gene Research, Yamaguchi University, 1–1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan;
- Kagoshima University (JP)
- Venue
- Molecular Biology of the Cell
- Published
- 2002-12
- Volume
- 13
- Issue
- 12
- Pages
- 4371-4387
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC138640
- OpenAlex
- W2099892653
- Cited by
- 141
- References
- 52
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 8 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science Society
- Directorate for Biological Sciences
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- DMT1, alternative splicing, protein isoforms, subcellular localization, iron absorption, endosomal trafficking, early endosomes, late endosomes, lysosomes, apical membrane, cell polarity, N-glycosylation, cytoplasmic tail, iron-responsive element, cell type-specific gene expression
- MeSH terms
- Solute Carrier Family 11, Member 2, Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cytoplasm, Detergents, Dogs, Electrophoresis, Polyacrylamide Gel, Epithelial Cells, Exons, Genetic Complementation Test, Glycosylation, Humans, Iron, Microscopy, Fluorescence, Models, Biological, Molecular Sequence Data, Phenotype, Plasmids, Schizosaccharomyces, Subcellular Fractions, Transfection, Tumor Cells, Cultured, Immunoblotting, Blotting, Western, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, Alternative Splicing, Protein Structure, Tertiary, Biotinylation, Protein Isoforms, Membrane Microdomains, Cation Transport Proteins, Iron-Binding Proteins, Mice, Rats
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