Abstract
The best known attribute of the prion protein (PrP) is its tendency to misfold into a rogue isoform. Much less understood is how this misfolded isoform causes deadly brain illnesses. Although neurodegeneration in prion disease is often seen as the result of abnormal PrP function, amazingly little is known about the normal, physiological role of PrP. In particular, the absence of obvious phenotypes in PrP knockout mice has prevented scientists from answering this important question. Using knockdown approaches, we previously produced clear PrP loss-of-function phenotypes in zebrafish. Analysis of these phenotypes revealed that PrP can modulate E-cadherin-based cell adhesion, thereby controlling essential morphogenetic cell movements in the early embryo. Our data also showed that PrP itself can elicit homophilic cell-cell adhesion and trigger intracellular signaling via Src-related kinases. Here we discuss the use of the zebrafish in prion biology, and how these findings may advance our understanding of the roles of PrP in health and disease.
Note
In a recent study, Salta et al. have provided the first evidence of neurodegeneration and plaque-like aggregates in the brains of fish fed with bovine and ovine prions.Citation35 These data highlight the need to ascertain the occurrence, transmissibility and infectivity of fish prions.