Divalent cation transporter

Fe2+ is also transported by the CorA protein (Hantke, 1997), a divalent cation transporter for Mg2+, Co2+, Mn2+, and Ni2+ in E. coli and S. typhimurium. CorA may represent the often-mentioned low-affinity iron-uptake system of E. coli that is suppressed in Fe3+ uptake studies by the addition of 0.2 mM dipyridyl and 0.1 mM nitrilotriacetate. 

Figure 8.3 A model of iron transport across the intestine. Reduction of ferric complexes to the ferrous form is achieved by the action of the brush border ferric reductase. The ferrous form is transported across the brush border membrane by the proton-coupled divalent cation transporter (DCT1) where it enters an unknown compartment in the cytosol. Ferrous iron is then transported across the basolateral membrane by IREG1, where the membrane-bound copper oxidase hephaestin (Hp) promotes release and binding of Fe3+ to circulating apotransferrin. Except for hephaestin the number of transmembrane domains for each protein is not shown in full. Reprinted from McKie et al., 2000. Copyright (2000), with permission from Elsevier Science.

The sarcoplasmic reticulum (SR) was first identified as the major mobilizable intracellular store of Ca2+ in skeletal muscles through the work of S. Ebashi, W. Hasselbach and A. Weber (review in Ebashi 1991). Identification of the SR and its role in smooth muscle met some early difficulties, partly due to the destructive effects of osmium fixation. Eventually the SR of smooth muscle was also identified, quantitated and its spatial distribution, peripheral and central, determined (Somlyo et al 1971, Devine et al 1971). Strontium (Sr), used as an electron opaque analogue of Ca2+, permitted direct, electron microscopic visualization of divalent cation transport into the SR (Somlyo Somlyo 1971). 

We will discuss in more detail in Chapter 8 how intracellular copper levels are maintained at extremely low levels by a series of copper chaperone proteins, which sequester newly assimilated copper within the cytoplasm of cells and deliver it in a targeted manner to be incorporated into specific copper-containing proteins. While copper uptake across the gastrointestinal tract is poorly understood—most probably utilising the divalent cation transporter... 

Of the body s daily iron uptake, 1-2 mg are absorbed in the duodenum and proximal jejunum. Resorption is pH-dependent Fe + is insoluble at a pH value of >4. Vitamin C enhances iron resorption (= reduction of iron and formation of a soluble iron-ascorbat chelate). DCT 1 (= divalent cation transporter) serves as a mucosa transporter and also supports mucosal transport of zinc, copper, cobalt etc. Iron facilitates O2 transport and the transfer of electrons. 

Copper uptake across the gastrointestinal tract is poorly understood — most probably utihsing the divalent cation transporter DMTl. At the cellular level, Cu is imported across the plasma membrane of mammalian cells as Cu, by members of the CTR family. The CTR family of proteins have been found in yeast and plants, as we saw, but also in humans and other mammals. They contain several methionine-rich motifs at their N-terminus, and conserved cysteine and histidine residues at their C-terminus. Unusually, CTR proteins can mediate the uptake of platinum anticancer drugs into mammalian cells (see Chapter 22). 

Agranoff, D., I.M. Monahan, J.A. Mangan, P.D. Butcher and S. Krishna. Mycobacterium tuberculosis expresses a novel pH-dependent divalent cation transporter belonging to the Nramp family. J. Exp. Med. 

Figure 13-2 Distribution of some elements shown separately in Figure 13-1 in some known tissue compartments, int, intestine hep, hepatocytes bm, bone marrow TfR, transferrin receptors in cells in bone marrow ly, lymphocytes. Lymphocytes ( ) are shown here in the liver. They belong, however, to a pool of cells continuously recirculating between blood and lymph. This could give them a preferential capacity of surveillance of sites where non-transferrin bound iron levels might be abnormally high. Divalent cation transporters represented here by DCTl may come to have important roles in the first step of iron entry into an organism through the intestinal epithelial cells.

Kolber, M. A., Haynes, D. H. Fluorescence Study of the Divalent Cation Transport Mechanism of A23187 in Phospholipid Membranes, Accepted for publication in Biophysical J., May, 1981 Ladbrooke, B. D., Chapman, D. Chem. Phys. Lipids 3, 304 (1969)... 

Hayashi, N., Ito, M., Horiike, S., Taguchi, H. (2001). Molecular cloning of a putative divalent-cation transporter gene as a new genetic marker for the identification of Lactobacillus brevis strains capable of growing in beer. Applied Microbiology and Biotechnology, 55, 596-603. 

A number of recent studies established the basis of the toxicokinetic interaction of Fe with Pb. This interaction appears to occur through operation of the divalent metal transporter 1 (DMTl), also known as the natural resistance-associated macrophage protein 2 (NRAMP2), the divalent cation transporter 1 (DCTl) (Bressler et al., 2004, 2007 Gu et al., 2009 Kayaalti et al., 2010 Mims and Prchal, 2005). 

LiD" " -I- L2 this transfer clearly suggests a mechanism for divalent cation transport. 

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