Figure 9.

Proposed mechanism of Fe transport at the BCB. Fe in the blood, as Tf-bound Fe³⁺, is transported by a TfR-mediated endocytosis across the basolateral membrane into the choroidal epithelial cells. Within endosomes, ferric Fe is reduced to ferrous Fe by oxidoreductase. Cellular Fe is then bound to ferroportin or MTP1, which functions to expel Fe into the CSF. In the opposite direction, free Fe in the CSF is taken up by DMT1 located in the apical membrane of the choroidal epithelial cell. In the Transwell model and under the normal condition, the DMT1-mediated Fe uptake at apical membrane may surpass the TfR-mediated transport from the basolateral side, serving as the normal process for Fe clearance in the CSF. Mn exposure in vitro, by increasing DMT1 expression, appears to facilitate the “efflux” of Fe from the CSF to the blood. However, under the in vivo condition, Mn exposure translocates MTP1 toward the apical microvilli of the choroid plexus (22) and activates the MTP1-mediated process to expel excess intracellular Fe toward apical CSF compartment. This process may offset DMT1-mediated Fe uptake on the apical membrane. The net in vivo result is a diminished Fe clearance by the choroid plexus and an increased Fe in the CSF. TfR, transferrin receptor; N, nucleus. A color version of this figure is available in the online journal.