Promiscuous functions of the prion protein family

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.