Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis

We previously demonstrated ferritin binding is specific to white matter in mouse and human brain tissue and is not found within Multiple Sclerotic pla ques. These results suggest that ferritin receptors are selectively express ed on oligodendrocytes. The present studies were designed to test the hypot hesis that oligodendrocyte progenitor cells selectively bind ferritin and i nternalize it by methods consistent with receptor-mediated endocytosis. Usi ng a cell culture system enriched for oligodendrocyte progenitor cells, we determined, that oligodendrocyte progenitor cells bind ferritin in a satura ble and competitive manner with a K-d of 5 nM and a receptor density of 0.0 6 fmol bound/ 20,000 cells. FITC tagged ferritin is internalized by A2B5, O 4 or CNPase expressing cells in the culture, but not by GFAP+ cells. The up take of ferritin into the oligodendrocyte progenitors was inhibited by trea ting the cells with inhibitors of receptor mediated endocytosis (hypertonic medium, potassium deficient medium, ATP depletion, sulfhydryl reagents). I n addition exogenous ferritin decreased iron responsive element/ iron regul atory protein binding indicating that the iron within the internalized ferr itin is released and contributes to the intracellular iron pool. Given the relatively high amount of iron that can be delivered via ferritin, and the selective distribution of ferritin receptors in the white matter tracts in vivo, we propose that ferritin is a major source of iron for oligodendrocyt es. J. Neurosci. Res. 61:52-60, 2000. (C) 2000 Wiley-Liss, Inc.