Polarized localization of vitamin C transporters, SVCT1 and SVCT2, in epithelial cells.
Messenger RNA of homologous sodium-vitamin C cotransporters, SVCT1 and SVCT2, were found in the intestine. Studies using cultured intestinal cells suggested an apical presence of SVCT1 but the function of SVCT2 was unknown. Here, we showed that enterocytes from heterozygous SVCT2-knockout mice had lower sodium-dependent vitamin C accumulation compared to those from the wildtype. Thus, SVCT2 appears to be functional in enterocytes. We then tested whether SVCT2 could have a redundant function as SVCT1 by constructing and expressing EGFP-tagged SVCTs in intestinal Caco-2 and kidney MDCK cells. In confluent epithelial cells, SVCT1 protein expressed predominantly on the apical membrane. SVCT2, in contrast, accumulated at the basolateral surface. Functionally, SVCT1 expression led to more transport activity from the apical membrane, while SVCT2 expression only increased the uptake under the condition when basolateral membrane was exposed. This differential epithelial membrane distribution and function suggests non-redundant functions of these two isoforms.
Boyer
James C
JC
Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, NY 14214, USA.
Campbell
Christine E
CE
Sigurdson
Wade J
WJ
Kuo
Shiu-Ming
SM
D000818:Animals; D001205:Ascorbic Acid / Q000493:pharmacokinetics*; D001693:Biological Transport, Active / Q000502:physiology; D016466:CHO Cells; D018938:Caco-2 Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D020895:Enterocytes / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000378:metabolism*; D014018:Tissue Distribution
D029363:Organic Anion Transporters, Sodium-Dependent; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; C555164:Slc23a1 protein, mouse; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid