Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1

被引:34
作者
Nunez, Marco T. [1 ,2 ]
Tapia, Victoria [1 ,2 ]
Rojas, Alejandro [2 ]
Aguirre, Pabla [2 ]
Gomez, Francisco [1 ,2 ]
Nualart, Francisco [3 ,4 ]
机构
[1] Univ Chile, Dept Biol, Fac Ciencias, Santiago 3425, Chile
[2] Cell Dynam & Biotechnol Inst, Santiago, Chile
[3] Fac Biol Sci, Dept Cell Biol, Santiago, Chile
[4] Univ Concepcion, Dept Cell Biol, Concepcion, Chile
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2010年 / 298卷 / 03期
关键词
intestinal iron absorption; divalent metal transporter 1; mucosal block; DIVALENT METAL TRANSPORTER-1; LABILE PLASMA IRON; CACO-2; CELLS; EPITHELIAL-CELLS; ABSORPTION; HEPCIDIN; TRAFFICKING; TRANSFERRIN; EXPRESSION; POOL;
D O I
10.1152/ajpcell.00168.2009
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nunez MT, Tapia V, Rojas A, Aguirre P, Gomez F, Nualart F. Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1. Am J Physiol Cell Physiol 298: C477-C485, 2010. First published December 9, 2009; doi: 10.1152/ajpcell.00168.2009.-Intestinal iron absorption comprises the coordinated activity of the influx transporter divalent metal transporter 1 (DMT1) and the efflux transporter ferroportin (FPN). In this work, we studied the movement of DMT1 and FPN between cellular compartments as a function of iron supply. In rat duodenum, iron gavage resulted in the relocation of DMT1 to basal domains and the internalization of basolateral FPN. Considerable FPN was also found in apical domains. In Caco-2 cells, the apical-to-basal movement of cyan fluorescent protein-tagged DMT1 was complete 90 min after the addition of iron. Steady-state membrane localization studies in Caco-2 cells revealed that iron status determined the apical/basolateral membrane distribution of DMT1 and FPN. In agreement with the membrane distribution of the transporters, Fe-55 flux experiments revealed inward and outward iron fluxes at both membrane domains. Antisense oligonucleotides targeted to DMT1 or FPN inhibited basolateral iron uptake and apical iron efflux, respectively, indicating the participation of DMT1 and FPN in these fluxes. The fluxes were regulated by the iron supply; increased iron reduced apical uptake and basal efflux and increased basal uptake and apical efflux. These findings suggest a novel mechanism of regulation of intestinal iron absorption based on inward and outward fluxes at both membrane domains, and repositioning of DMT1 and FPN between membrane and intracellular compartments as a function of iron supply. This mechanism should be complementary to those based in the transcriptional or translational regulation of iron transport proteins.
引用
收藏
页码:C477 / C485
页数:9
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