title: An emerging role of the cellular prion protein as a modulator of a morphogenetic program underlying epithelial-to-mesenchymal transition.
abstract: Knowledge of phenotypic changes the cellular prion protein (PrP(C)) contributes to may provide novel avenues for understanding its function. Here we consider data from functional knockout/down studies and protein-protein interaction analyses from the perspective of PrP's relationship to its ancestral ZIP metal ion transporting proteins. When approached in this manner, a role of PrP(C) as a modulator of a complex morphogenetic program that underlies epithelial-to-mesenchymal transition (EMT) emerges. To execute EMT, cells have to master the challenge to shift from cell-cell to cell-substrate modes of adherence. During this process, cell-cell junctions stabilized by E-cadherins are replaced by focal adhesions that mediate cell-substrate contacts. A similar reprogramming occurs during distinct organogenesis events that have been shown to rely on ZIP transporters. A model is presented that sees ZIP transporters, and possibly also PrP(C), affect this balance of adherence modes at both the transcriptional and post-translational levels.
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada.
authors.forename: Mohadeseh
authors.initials: M
authors.lastname: Mehrabian
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada.
authors.forename: Sepehr
authors.initials: S
authors.lastname: Ehsani
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada.
authors.forename: Gerold
authors.initials: G
authors.lastname: Schmitt-Ulms
keywords: ZIP transporter; epithelial-to-mesenchymal transition; function; phenotype; prion protein