Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc

The cellular prion protein has been identified as a metalloprotein that binds copper. There have been some suggestions that prion protein also influences zinc and manganese homeostasis. In this study we used a series of cell lines to study the levels of zinc and manganese under different conditions. We overexpressed either the prion protein or known transporters for zinc and manganese to determine relations between the prion protein and both manganese and zinc homeostasis. Our observations supported neither a link between the prion protein and zinc metabolism nor any effect of altered zinc levels on prion protein expression or cellular infection with prions. In contrast we found that a gain of function mutant of a manganese transporter caused reduction of manganese levels in prion infected cells, loss of observable PrPSc in cells and resistance to prion infection. These studies strengthen the link between manganese and prion disease. •We studied the impact of PrP expression on levels of zinc and manganese in cells.•We found no relation between the prion protein and zinc metabolism.•Prion infected cells have higher levels of manganese.•A mutant manganese transporter diminishes manganese in prion infected cells.•Reduction of manganese in cells cures them of prion infection.