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

摘要

00168.2009.—Intestinal iron absorption comprisesthe coordinated activity of the influx transporter divalent metaltransporter 1 (DMT1) and the efflux transporter ferroportin (FPN). Inthis work, we studied the movement of DMT1 and FPN betweencellular compartments as a function of iron supply. In rat duodenum,iron gavage resulted in the relocation of DMT1 to basal domains andthe internalization of basolateral FPN. Considerable FPN was alsofound in apical domains. In Caco-2 cells, the apical-to-basal movementof cyan fluorescent protein-tagged DMT1 was complete 90 minafter the addition of iron. Steady-state membrane localization studiesin Caco-2 cells revealed that iron status determined the apical/basolateral membrane distribution of DMT1 and FPN. In agreementwith the membrane distribution of the transporters, 55Fe flux experimentsrevealed inward and outward iron fluxes at both membranedomains. Antisense oligonucleotides targeted to DMT1 or FPN inhibitedbasolateral iron uptake and apical iron efflux, respectively, indicatingthe participation of DMT1 and FPN in these fluxes. The fluxeswere regulated by the iron supply; increased iron reduced apicaluptake and basal efflux and increased basal uptake and apical efflux.These findings suggest a novel mechanism of regulation of intestinaliron absorption based on inward and outward fluxes at both membranedomains, and repositioning of DMT1 and FPN between membraneand intracellular compartments as a function of iron supply. Thismechanism should be complementary to those based in the transcriptionalor translational regulation of iron transport proteins.