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Copper and zinc cause delivery of the prion protein from the plasma membrane to a subset of early endosomes and the Golgi
Author(s) -
Brown Lesley R.,
Harris David A.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01996.x
Subject(s) - endosome , golgi apparatus , endocytosis , microbiology and biotechnology , transferrin , intracellular , glycoprotein , transferrin receptor , chemistry , membrane glycoproteins , transport protein , biology , biochemistry , biophysics , cell , endoplasmic reticulum
The cellular isoform of prion protein (PrP C ) is a plasma membrane glycoprotein whose conformational conversion into PrP Sc is the central molecular event in the propagation of infectious prions. However, the physiological function of PrP C has remained uncertain. The finding that PrP C binds copper ions with low micromolar affinity, coupled with several other observations, has led to the proposal that the protein plays a role in copper homeostasis. Using biochemical techniques, we had shown previously that copper ions rapidly and reversibly stimulate endocytosis of PrP C from the cell surface. In this report, we employ immunofluorescence microscopy to further investigate the specificity and kinetics of metal effects on PrP C trafficking and to identify the intracellular compartments to which internalized PrP C is delivered in response to copper and zinc. We find that both of these metals stimulate redistribution of surface PrP C to a subset of transferrin‐containing early endosomes as well as to Golgi compartments. These results are consistent with models in which PrP C plays a role in the cellular uptake or efflux of transition metals.