Promiscuous functions of the prion protein family.

Sophie Mouillet-Richard,Jean-Luc Vilotte

doi:10.3389/fcell.2015.00007

Abstract

From the discovery nearly 30 years ago of the cellular prion protein PrPC, the founder of the prion protein family, there has been a constant quest to dissect its biological function and that of its two homologs, Doppel and Shadoo. While clues were greatly anticipated from the generation of PrP null mice, alterations appeared quite imperceptible at first examination, beyond the clear-cut resistance to prion infection. Taking a closer look at these knockout mice, together with the generation of mice invalidated for Doppel and Shadoo has in the end yielded much information on the -sometimes overlapping- roles of these proteins. These in-depth investigations have also explored functions of the prion protein family beyond the central nervous system, which was obviously the first focus of interest since prion diseases are neurodegenerative disorders. This Frontiers Research topic on the promiscuous functions of the prion protein family incorporates contributions ranging from the field of developmental biology to that of structure-function, including aspects related to cell biology, signal transduction, and neuronal homeostasis.

Highlights

Starting from the embryo, the contribution by Halliez et al provides a comprehensive review of the impact of PrP invalidation on embryonic development, compiling data from both mice and zebrafish and highlighting the key cellular pathways affected by PrPC deletion (Halliez et al, 2014)
It summarizes the recent data obtained with the help of PrP invalidated mice and discusses the pathophysiological implications stemming from the aberrant PrPC expression in human gestational diseases
Mehrabian et al provide a perspective on the potential relationship between PrPC and the pathways involved in epithelial to mesenchymal transition, a process associated with major changes in cell adhesion properties and that physiologically takes place during embryonic development, while involved in cancer metastasis (Mehrabian et al, 2014)

Summary

Introduction

Starting from the embryo, the contribution by Halliez et al provides a comprehensive review of the impact of PrP invalidation on embryonic development, compiling data from both mice and zebrafish and highlighting the key cellular pathways affected by PrPC deletion (Halliez et al, 2014). It summarizes the recent data obtained with the help of PrP invalidated mice and discusses the pathophysiological implications stemming from the aberrant PrPC expression in human gestational diseases.

Results

Conclusion