Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Canonne-Hergaux, F.
Right arrow Articles by Gros, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Canonne-Hergaux, F.
Right arrow Articles by Gros, P.
Related Collections
Right arrow Red Cells
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

Blood, Vol. 93 No. 12 (June 15), 1999: pp. 4406-4417

Cellular and Subcellular Localization of the Nramp2 Iron Transporter in the Intestinal Brush Border and Regulation by Dietary Iron

F. Canonne-Hergaux, S. Gruenheid, P. Ponka, and P. Gros

From the Departments of Biochemistry and Physiology, McGill University, Montreal, Quebec, Canada; and the Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.

Genetic studies in animal models of microcytic anemia and biochemical studies of transport have implicated the Nramp2 gene in iron transport. Nramp2 generates two alternatively spliced mRNAs that differ at their 3' untranslated region by the presence or absence of an iron-response element (IRE) and that encode two proteins with distinct carboxy termini. Antisera raised against Nramp2 fusion proteins containing either the carboxy or amino termini of Nramp2 and that can help distinguish between the two Nramp2 protein isoforms (IRE: isoform I; non-IRE: isoform II) were generated. These antibodies were used to identify the cellular and subcellular localization of Nramp2 in normal tissues and to study possible regulation by dietary iron deprivation. Immunoblotting experiments with membrane fractions from intact organs show that Nramp2 is expressed at low levels throughout the small intestine and to a higher extent in kidney. Dietary iron starvation results in a dramatic upregulation of the Nramp2 isoform I in the proximal portion of the duodenum only, whereas expression in the rest of the small intestine and in kidney remains largely unchanged in response to the lack of dietary iron. In proximal duodenum, immunostaining studies of tissue sections show that Nramp2 protein expression is abundant under iron deplete condition and limited to the villi and is absent in the crypts. In the villi, staining is limited to the columnar absorptive epithelium of the mucosa (enterocytes), with no expression in mucus-secreting goblet cells or in the lamina propria. Nramp2 expression is strongest in the apical two thirds of the villi and is very intense at the brush border of the apical pole of the enterocytes, whereas the basolateral membrane of these cells is negative for Nramp2. These results strongly suggest that Nramp2 is indeed responsible for transferrin-independent iron uptake in the duodenum. These findings are discussed in the context of overall mechanisms of iron acquisition by the body.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
BloodHome page
N. C. Andrews
Forging a field: the golden age of iron biology
Blood, July 15, 2008; 112(2): 219 - 230.
[Full Text] [PDF]


Home page
Poult. Sci.Home page
S. P. Bai, L. Lu, X. G. Luo, and B. Liu
Cloning, Sequencing, Characterization, and Expressions of Divalent Metal Transporter One in the Small Intestine of Broilers
Poult. Sci., April 1, 2008; 87(4): 768 - 776.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M. E. Techau, J. Valdez-Taubas, J.-F. Popoff, R. Francis, M. Seaman, and J. M. Blackwell
Evolution of Differences in Transport Function in Slc11a Family Members
J. Biol. Chem., December 7, 2007; 282(49): 35646 - 35656.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. Thompson, R. M. Molina, T. Donaghey, J. D. Brain, and M. Wessling-Resnick
Iron absorption by Belgrade rat pups during lactation
Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G640 - G644.
[Abstract] [Full Text] [PDF]


Home page
Exp PhysiolHome page
D. T. Thwaites and C. M. H. Anderson
H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine
Exp Physiol, July 1, 2007; 92(4): 603 - 619.
[Abstract] [Full Text] [PDF]


Home page
FASEB J.Home page
K. Thompson, R. M. Molina, T. Donaghey, J. E. Schwob, J. D. Brain, and M. Wessling-Resnick
Olfactory uptake of manganese requires DMT1 and is enhanced by anemia
FASEB J, January 1, 2007; 21(1): 223 - 230.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
P. Kaler and R. Prasad
Molecular cloning and functional characterization of novel zinc transporter rZip10 (Slc39a10) involved in zinc uptake across rat renal brush-border membrane
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F217 - F229.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
S. Lam-Yuk-Tseung, V. Picard, and P. Gros
Identification of a Tyrosine-based Motif (YGSI) in the Amino Terminus of Nramp1 (Slc11a1) That Is Important for Lysosomal Targeting
J. Biol. Chem., October 20, 2006; 281(42): 31677 - 31688.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Med.Home page
C. Huynh, D. L. Sacks, and N. W. Andrews
A Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes
J. Exp. Med., October 2, 2006; 203(10): 2363 - 2375.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
M. Abouhamed, J. Gburek, W. Liu, B. Torchalski, A. Wilhelm, N. A. Wolff, E. I. Christensen, F. Thevenod, and C. P. Smith
Divalent metal transporter 1 in the kidney proximal tubule is expressed in late endosomes/lysosomal membranes: implications for renal handling of protein-metal complexes
Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1525 - F1533.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Beaumont, J. Delaunay, G. Hetet, B. Grandchamp, M. de Montalembert, and G. Tchernia
Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload
Blood, May 15, 2006; 107(10): 4168 - 4170.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Y. Ma, M. Yeh, K.-y. Yeh, and J. Glass
Iron Imports. V. Transport of iron through the intestinal epithelium
Am J Physiol Gastrointest Liver Physiol, March 1, 2006; 290(3): G417 - G422.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
Y.-Z. Chang, Y. Ke, J.-R. Du, G. M. Halpern, K.-P. Ho, L. Zhu, X.-S. Gu, Y.-J. Xu, Q. Wang, L.-Z. Li, et al.
Increased Divalent Metal Transporter 1 Expression Might Be Associated with the Neurotoxicity of L-DOPA
Mol. Pharmacol., March 1, 2006; 69(3): 968 - 974.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
E. M. Leslie, J. Liu, C. D. Klaassen, and M. P. Waalkes
Acquired Cadmium Resistance in Metallothionein-I/II(-/-) Knockout Cells: Role of the T-Type Calcium Channel Cacn{alpha}1G in Cadmium Uptake
Mol. Pharmacol., February 1, 2006; 69(2): 629 - 639.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. J. Smyth, A. Glanfield, D. P. McManus, E. Hacker, D. Blair, G. J. Anderson, and M. K. Jones
Two Isoforms of a Divalent Metal Transporter (DMT1) in Schistosoma mansoni Suggest a Surface-associated Pathway for Iron Absorption in Schistosomes
J. Biol. Chem., January 27, 2006; 281(4): 2242 - 2248.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
F. Canonne-Hergaux, A. Donovan, C. Delaby, H.-j. Wang, and P. Gros
Comparative studies of duodenal and macrophage ferroportin proteins
Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G156 - G163.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Iolascon, M. d'Apolito, V. Servedio, F. Cimmino, A. Piga, and C. Camaschella
Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2)
Blood, January 1, 2006; 107(1): 349 - 354.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
W.S. Chong, P.C. Kwan, L.Y. Chan, P.Y. Chiu, T.K. Cheung, and T.K. Lau
Expression of divalent metal transporter 1 (DMT1) isoforms in first trimester human placenta and embryonic tissues
Hum. Reprod., December 1, 2005; 20(12): 3532 - 3538.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Delaby, N. Pilard, A. S. Goncalves, C. Beaumont, and F. Canonne-Hergaux
Presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and down-regulated by hepcidin
Blood, December 1, 2005; 106(12): 3979 - 3984.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. Priwitzerova, G. Nie, A. D. Sheftel, D. Pospisilova, V. Divoky, and P. Ponka
Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake
Blood, December 1, 2005; 106(12): 3985 - 3987.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. Galy, D. Ferring, B. Minana, O. Bell, H. G. Janser, M. Muckenthaler, K. Schumann, and M. W. Hentze
Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)
Blood, October 1, 2005; 106(7): 2580 - 2589.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
F. Yang, D. J. Haile, X. Wang, L. A. Dailey, J. G. Stonehuerner, and A. J. Ghio
Apical location of ferroportin 1 in airway epithelia and its role in iron detoxification in the lung
Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L14 - L23.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
L. Viatte, J.-C. Lesbordes-Brion, D.-Q. Lou, M. Bennoun, G. Nicolas, A. Kahn, F. Canonne-Hergaux, and S. Vaulont
Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice
Blood, June 15, 2005; 105(12): 4861 - 4864.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
A. Fortier, G. Min-Oo, J. Forbes, S. Lam-Yuk-Tseung, and P. Gros
Single gene effects in mouse models of host: pathogen interactions
J. Leukoc. Biol., June 1, 2005; 77(6): 868 - 877.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. F. Collins, C. A. Franck, K. V. Kowdley, and F. K. Ghishan
Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum
Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G964 - G971.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. Heilig, R. Molina, T. Donaghey, J. D. Brain, and M. Wessling-Resnick
Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats
Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L887 - L893.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
W.-I. Leong and B. Lonnerdal
Iron transporters in rat mammary gland: effects of different stages of lactation and maternal iron status
Am. J. Clinical Nutrition, February 1, 2005; 81(2): 445 - 453.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. P. Mims, Y. Guan, D. Pospisilova, M. Priwitzerova, K. Indrak, P. Ponka, V. Divoky, and J. T. Prchal
Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload
Blood, February 1, 2005; 105(3): 1337 - 1342.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
K. P. Griffin, D. T. Ward, W. Liu, G. Stewart, I. D. Morris, and C. P. Smith
Differential expression of divalent metal transporter DMT1 (Slc11a2) in the spermatogenic epithelium of the developing and adult rat testis
Am J Physiol Cell Physiol, January 1, 2005; 288(1): C176 - C184.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
R. A. White, S. G. McNulty, S. Roman, U. Garg, E. Wirtz, D. Kohlbrecher, N. N. Nsumu, D. Pinson, R. Gaedigk, K. Blackmore, et al.
Chromosomal localization, hematologic characterization, and iron metabolism of the hereditary erythroblastic anemia (hea) mutant mouse
Blood, September 1, 2004; 104(5): 1511 - 1518.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
N. Touret, N. Martin-Orozco, P. Paroutis, W. Furuya, S. Lam-Yuk-Tseung, J. Forbes, P. Gros, and S. Grinstein
Molecular and cellular mechanisms underlying iron transport deficiency in microcytic anemia
Blood, September 1, 2004; 104(5): 1526 - 1533.
[Abstract] [Full Text] [PDF]


Home page
Physiol. GenomicsHome page
D. Barisani, A. Parafioriti, M. T. Bardella, H. Zoller, D. Conte, E. Armiraglio, C. Trovato, R. O. Koch, and G. Weiss
Adaptive changes of duodenal iron transport proteins in celiac disease
Physiol Genomics, May 19, 2004; 17(3): 316 - 325.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
W.-I. Leong, C. L Bowlus, J. Tallkvist, and B. Lonnerdal
Iron supplementation during infancy--effects on expression of iron transporters, iron absorption, and iron utilization in rat pups
Am. J. Clinical Nutrition, December 1, 2003; 78(6): 1203 - 1211.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W.-I. Leong, C. L. Bowlus, J. Tallkvist, and B. Lonnerdal
DMT1 and FPN1 expression during infancy: developmental regulation of iron absorption
Am J Physiol Gastrointest Liver Physiol, December 1, 2003; 285(6): G1153 - G1161.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. R. Forbes and P. Gros
Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane
Blood, September 1, 2003; 102(5): 1884 - 1892.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
N. Touret, W. Furuya, J. Forbes, P. Gros, and S. Grinstein
Dynamic Traffic through the Recycling Compartment Couples the Metal Transporter Nramp2 (DMT1) with the Transferrin Receptor
J. Biol. Chem., July 3, 2003; 278(28): 25548 - 25557.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
J. Yang, K. Mori, J. Y. Li, and J. Barasch
Iron, lipocalin, and kidney epithelia
Am J Physiol Renal Physiol, July 1, 2003; 285(1): F9 - F18.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
N. Jabado, P. Cuellar-Mata, S. Grinstein, and P. Gros
Iron chelators modulate the fusogenic properties of Salmonella-containing phagosomes
PNAS, May 13, 2003; 100(10): 6127 - 6132.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Lam-Yuk-Tseung, G. Govoni, J. Forbes, and P. Gros
Iron transport by Nramp2/DMT1: pH regulation of transport by 2 histidines in transmembrane domain 6
Blood, May 1, 2003; 101(9): 3699 - 3707.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. G. Gehrke, H.-D. Riedel, T. Herrmann, B. Hadaschik, K. Bents, C. Veltkamp, and W. Stremmel
UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is closely related to SFT, a stimulator of iron transport, and is up-regulated in hereditary hemochromatosis
Blood, April 15, 2003; 101(8): 3288 - 3293.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
R J Simpson, E Debnam, N Beaumont, S Bahram, K Schumann, and S K S Srai
Duodenal mucosal reductase in wild-type and Hfe knockout mice on iron adequate, iron deficient, and iron rich feeding
Gut, April 1, 2003; 52(4): 510 - 513.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
D M Frazer, S J Wilkins, E M Becker, T L Murphy, C D Vulpe, A T McKie, and G J Anderson
A rapid decrease in the expression of DMT1 and Dcytb but not Ireg1 or hephaestin explains the mucosal block phenomenon of iron absorption
Gut, March 1, 2003; 52(3): 340 - 346.
[Abstract] [Full Text] [PDF]


</