Cellular location of proteins related to iron absorption and transport

Simovich, Marcia J.; Conrad, Marcel E.; Umbreit, Jay N.; Moore, Elizabeth; Hainsworth, Lucille N.; Smith, Hilary K.

doi:10.1002/ajh.10052.abs

Cited by 10 publications

(10 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Whereas it is difficult to visualize the protein in normal cells, the iron-deficient duodenal cells have dramatic staining for DMT-1 along the cell surface of the villae [14,32]. Mobilferrin levels are not increased in the intestinal mucosa with iron deficiency, but in tissue culture cells and in the duodenum the protein appears to increase at the villae cell surface [13,33].…”

Section: Discussionmentioning

confidence: 99%

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

et al. 2003

Self Cite

View full text Add to dashboard Cite

There are two pathways for inorganic iron uptake in the intestine, the ferric pathway, mediated by the key protein mobilferrin, and the ferrous pathway, mediated by DMT-1. Previous studies reported that the amount of DMT-1 increased in the intestinal mucosa in iron deficiency and the increase was seen in the apical portion of the villus of the duodenal mucosa. Mobilferrin did not quantitatively increase but became localized at the cell membrane. However, studies on fresh tissue have not previously been performed and the localization to the microvillae has not been demonstrated. In order to more definitively localize these proteins immunofluorescent and electron microscopic studies were undertaken. Samples were also subjected to biochemical analysis and Western analysis. In iron-deficient animals both DMT-1 and Mobilferrin were concentrated in the apical surface of the villae. Electron microscopy revealed that the majority of this increase in the amount of these proteins near the luminal surface was due to increased binding of the proteins to mucin in vesicles near the surface. A significant portion of the iron transport proteins was localized in the goblet cells and outside the cell in the luminal mucin, as demonstrated by immunofluorescence, electron microscopy, and isolation of the mucin by cesium chloride gradient centrifugation and Western analysis. A new model for the transport of metal ions was suggested. The metal transport proteins travel from vesicles inside the cell out to the lumen mucin. This increases the surface area and allows a greater portion of the lumen contents to be exposed to the binding proteins. Once the metal is bound to the externalized protein it is internalized into the cell. This explains many of the unique properties of the iron-binding proteins and suggests that it may be a more general model for the absorption of other nutrients. Am. J. Hematol. 74:32-45, 2003.

show abstract

Section: Discussionmentioning

confidence: 99%

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…Immunolocalization experiments in IEC-6 cells isolated from the small intestine have identified hephaestin in the perinuclear region of the cells. Although this protein has also been detected on the plasma membrane, the labeling was weak and the exact region of membrane to which it is localized was not determined (Frazer et al, 2001;Simovich et al, 2002). It has been suggested that this protein may mediate the intracellular transport of Fe, and possibly Cd 2+ , to MTP1.…”

Section: Mimicry and Intestinal Transport Of CD 2+mentioning

confidence: 99%

Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

667

460

View full text Add to dashboard Cite

Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

show abstract

“…However, DMT1 might be part of the integrin-␤ 3 -mobilferrin pathway (118), suggesting that it may modify DMT1 specificity. Whether these components transport iron from the cell surface or from endosomes is presently not clear, because most of these proteins are intracellular (107).…”

Section: Many Solutions To the Problem Of Iron Transportmentioning

confidence: 99%

Iron, lipocalin, and kidney epithelia

Yang

Mori

et al. 2003

American Journal of Physiology-Renal Physiology

125

105

View full text Add to dashboard Cite

Brilliant new discoveries in the field of iron metabolism have revealed novel transmembrane iron transporters, novel hormones that regulate iron traffic, and iron's control of gene expression. An important role for iron in the embryonic kidney was first identified by Ekblom, who studied transferrin (Landschulz W and Ekblom P. J Biol Chem 260: 15580-15584, 1985; Landschulz W, Thesleff I, and Ekblom P. J Cell Biol 98: 596-601, 1984; Thesleff I, Partanen AM, Landschulz W, Trowbridge IS, and Ekblom P. Differentiation 30: 152-158, 1985). Nevertheless, how iron traffics to developing organs remains obscure. This review discusses a member of the lipocalin superfamily, 24p3 or neutrophil gelatinase-associated lipocalcin (NGAL), which induces the formation of kidney epithelia. We review the data showing that lipocalins transport low-molecular-weight chemical signals and data indicating that 24p3/NGAL transports iron. We compare 24p3/NGAL to transferrin and a variety of other iron trafficking pathways and suggest specific roles for each in iron transport. metanephric mesenchyme; induction; neutrophil gelatinase-associated lipocalin; NGAL; 24p3; transferrin; embryo THE KIDNEY FORMS FROM THE interaction of an epithelial tubule called the ureteric bud and metanephric mesenchymal cells (103). The ureteric bud produces the collecting ducts, whereas the mesenchymal cells produce the glomeruli and tubules of the nephron. Mesenchymal cells convert into epithelia and form nephrons after receiving signals from the ureteric bud (15,29,42,44,61,71,103,106,115,116,119). The ureteric bud has been shown to control the growth of the mesenchyme (for example, by FGFs) (4, 92), the expression of the essential Wnt-4 gene (for example, by Wnt-6) (60), and the expression of cohorts of epithelial proteins [for example, by leukemia inhibitory factor (LIF)] (6, 95).In this review, we describe a new ureteric bud protein called 24p3 (mouse) or neutrophil gelatinase-associated lipocalcin (NGAL; human) and review its relatives in the lipocalin superfamily. 24p3/NGAL induces epithelial development, but it neither targets the same mesenchymal cells as Wnt-6/Wnt-4 or LIF, nor does it activate the same type of signaling mechanism. We hypothesize that 24p3/NGAL is a novel signaling molecule and iron transporter, and we speculate that it is a new member of the non-transferrin-bound iron pool (NTBI). We describe general mechanisms of iron transport and the settings in which 24p3/NGAL and the NTBI pool are active. Last, we compare iron transport in the developing and adult kidney. Iron metabolism in fetal development is topical: 18% of human pregnancies in the industrialized countries are iron deficient, as are 38-55% of pregnancies in Africa and 62-88% in India, and worldwide the total affected births may near one billion (14). However, because little is known about embryonic mechanisms of iron handling, we have included a number of hypotheses and suggested experiments. 24p3/NGAL INDUCES EPITHELIATo identify novel ureteric bud factors that activate the m...

show abstract

Cellular location of proteins related to iron absorption and transport

Cited by 10 publications

References 16 publications

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

Molecular and ionic mimicry and the transport of toxic metals

Iron, lipocalin, and kidney epithelia

Contact Info

Product

Resources

About