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

University of California, Irvine, Irvine, California, United States
Biochemical Journal (Impact Factor: 4.4). 12/2003; 376(Pt 1):43-8. DOI: 10.1042/BJ20031220
Source: PubMed


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.

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Available from: Jonathan Marchant, Dec 13, 2013
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    • "There was polarization of both THTR-1 and THTR-2 to the apical membranes of hPTECs. Previous studies have detected THTR-1 protein in both basolateral and apical membranes of the proximal tubular epithelium and THTR-2 protein only in apical membranes [26], [27]. Therefore, thiamine likely crosses the human proximal tubular epithelium by THTR-1 and THTR-2 mediated uptake on the apical side and efflux on the basolateral side mainly by THTR-1 (Figure 4). "
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    ABSTRACT: Increased renal clearance of thiamine (vitamin B(1)) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: -76% and -53% respectively, p<0.001; transporter protein -77% and -83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy.
    Full-text · Article · Dec 2012 · PLoS ONE
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    • "The pattern of distribution of the TH and TH derivates transporters may play a significant role in establishing and maintaining the tissue distribution of TH (Boulware, Subramanian et al. 2003; Subramanian, Marchant et al. 2003; Said, Balamurugan et al. 2004; Miyajima and Kono 2010). The intestinal absorption of TH occurs mainly in the proximal small intestine by an active saturable mechanism and probably also by passive diffusion. "

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