title: Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc.
abstract: 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 PrP(Sc) in cells and resistance to prion infection. These studies strengthen the link between manganese and prion disease.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Pass
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Frudd
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Barnett
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, UK.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Blindauer
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, UK. Electronic address: bssdrb@bath.ac.uk.
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019286:Endopeptidase K / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics*; D011328:Prions / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015032:Zinc / Q000378:metabolism; D000097809:Transcription Factor MTF-1
chemical_list: D000252:Calcium-Transporting ATPases; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D019286:Endopeptidase K; D008345:Manganese; D026901:Membrane Transport Proteins; D011328:Prions; D018091:Receptors, AMPA; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C485803:Slc30a1 protein, mouse; C492024:Atp2c1 protein, mouse
keywords: Manganese; Prion; SPCA; Zinc; ZnT-1