Article

Polarized expression of members of the solute carrier SLC19A gene family of water-soluble multivitamin transporters: implications for physiological function.

Department of Pharmacology, 321 Church Street SE, University of Minnesota Medical School, MN 55455, USA.
Biochemical Journal (Impact Factor: 4.65). 12/2003; 376(Pt 1):43-8. DOI: 10.1042/BJ20031220
Source: PubMed

ABSTRACT Humans lack biochemical pathways for the synthesis of the micro-nutrients thiamine and folate. Cellular requirements are met through membrane transport activity, which is mediated by proteins of the SLC19A gene family. By using live-cell confocal imaging methods to resolve the localization of all SLC19A family members, we show that the two human thiamine transporters are differentially targeted in polarized cells, establishing a vectorial transport system. Such polarization decreases functional redundancy between transporter isoforms and allows for independent regulation of thiamine import and export pathways in cells.

0 Bookmarks
 · 
49 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Milk nutrients are secreted by epithelial cells in the alveoli of the mammary gland by several complex and highly coordinated systems. Many of these nutrients are transported from the blood to the milk via transcellular pathways that involve the concerted activity of transport proteins on the apical and basolateral membranes of mammary epithelial cells. In this review, we focus on transport mechanisms that contribute to the secretion of calcium, trace minerals and water soluble vitamins into milk with particular focus on the role of transporters of the SLC series as well as calcium transport proteins (ion channels and pumps). Numerous members of the SLC family are involved in the regulation of essential nutrients in the milk, such as the divalent metal transporter-1 (SLC11A2), ferroportin-1 (SLC40A1) and the copper transporter CTR1 (SLC31A1). A deeper understanding of the physiology and pathophysiology of these transporters will be of great value for drug discovery and treatment of breast diseases.
    Journal of Mammary Gland Biology and Neoplasia 02/2014; · 7.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thiamine, in the form of thiamine pyrophosphate, is a cofactor for a number of enzymes which play important roles in energy metabolism. Although dietary thiamine deficiency states have long been recognised, it is only relatively recently that inherited defects in thiamine uptake, activation and the attachment of the active cofactor to target enzymes have been described, and the underlying genetic defects identified. Thiamine is transported into cells by two carriers, THTR1 and THTR2, and deficiency of these results in thiamine-responsive megaloblastic anaemia and biotin-responsive basal ganglia disease respectively. Defective synthesis of thiamine pyrophosphate has been found in a small number of patients with episodic ataxia, delayed development and dystonia, while impaired transport of thiamine pyrophosphate into the mitochondrion is associated with Amish lethal microcephaly in most cases. In addition to defects in thiamine uptake and metabolism, patients with pyruvate dehydrogenase deficiency and maple syrup urine disease have been described who have a significant clinical and/or biochemical response to thiamine supplementation. In these patients, an intrinsic structural defect in the target enzymes reduces binding of the cofactor and this can be overcome at high concentrations. In most cases, the clinical and biochemical abnormalities in these conditions are relatively non-specific, and the range of recognised presentations is increasing rapidly at present as new patients are identified, often by genome sequencing. These conditions highlight the value of a trial of thiamine supplementation in patients whose clinical presentation falls within the spectrum of documented cases.
    Journal of Inherited Metabolic Disease 05/2014; · 4.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The reduced folate carrier (RFC, SLC19A1), thiamine transporter-1 (ThTr1, SLC19A2) and thiamine transporter-2 (ThTr2, SLC19A3) evolved from the same family of solute carriers. SLC19A1 transports folates but not thiamine. SLC19A2 and SLC19A3 transport thiamine but not folates. SLC19A1 and SLC19A2 deliver their substrates to systemic tissues; SLC19A3 mediates intestinal thiamine absorption. The proton-coupled folate transporter (PCFT, SLC46A1) is the mechanism by which folates are absorbed across the apical-brush-border membrane of the proximal small intestine. Two folate receptors (FOLR1 and FOLR2) mediate folate transport across epithelia by an endocytic process. Folate transporters are routes of delivery of drugs for the treatment of cancer and inflammatory diseases. There are autosomal recessive disorders associated with mutations in genes encoded for SLC46A1 (hereditary folate malabsorption), FOLR1 (cerebral folate deficiency), SLC19A2 (thiamine-responsive megaloblastic anemia), and SLC19A3 (biotin-responsive basal ganglia disease).
    Molecular Aspects of Medicine 04/2013; 34(2-3):373-385. · 10.38 Impact Factor

Full-text (2 Sources)

Download
4 Downloads
Available from
Jun 3, 2014