Prion protein localizes at the ciliary base during neural and cardiovascular development, and its depletion affects...

Although conversion of the cellular form of the prion protein (PrP(C)) into a misfolded isoform is the underlying cause of prion diseases, understanding PrP(C) physiological functions has remained challenging. PrP(C) depletion or overexpression alters the proliferation and differentiation properties of various types of stem and progenitor cells in vitro by unknown mechanisms. Such involvement remains uncertain in vivo in the absence of any drastic phenotype of mice lacking PrP(C). Here, we report PrP(C) enrichment at the base of the primary cilium in stem and progenitor cells from the central nervous system and cardiovascular system of developing mouse embryos. PrP(C) depletion in a neuroepithelial cell line dramatically altered key cilium-dependent processes, such as Sonic hedgehog signalling and α-tubulin post-translational modifications. These processes were also affected over a limited time window in PrP(C)-ablated embryos. Thus, our study reveals PrP(C) as a potential actor in the developmental regulation of microtubule dynamics and ciliary functions.