Apotransferrin and holotransferrin undergo different endocytic cycles in intestinal epithelia (Caco-2) cells

Abstract

Previous studies have demonstrated that diferric transferrin and apotransferrin compete for the binding to basolateral transfertin receptors and that transferrin-mediated iron uptake by Caco-2 cells is inhibited by apotransferrin to a larger extent than that predicted solely by receptor competition. This inhibition can have important implications in determining the net exchange of iron between intestinal cells and the basolateral milieu. Accordingly, we further characterized the endocytic cycles of apotransferrin and diferric transferrin in Caco-2 cells. We found that after internalization both apotransferrin and diferric transferrin recycled to the cell exterior, but that apotransferrin had a protracted endocytic cycle. Confocal microscopy studies revealed a different cellular distribution of apotransferrin and diferric transferrin; both were found in a compartment close to the basal membrane, but apotransferrin reached as well regions closer to the apical membrane. Moreover, the intr