An emerging role of the cellular prion protein as a modulator of a morphogenetic program underlying epithelial-to-mesenchymal transition

Abstract

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Knowledge of phenotypic changes the cellular prion protein (PrPC) 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 PrPC 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 PrPC, affect this balance of adherence modes at both the transcriptional and post-translational levels.

Keywords

• prion protein
• phenotype
• function
• epithelial-to-mesenchymal transition
• ZIP transporter