title: Prion protein localizes at the ciliary base during neural and cardiovascular development, and its depletion affects α-tubulin post-translational modifications.
abstract: 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.
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Halliez
authors.affiliation: INSERM UMR-S1124, Université Paris Descartes 75006, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Martin-Lannerée
authors.affiliation: INRA, UMR1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Passet
authors.affiliation: INSERM UMR-S1124, Université Paris Descartes 75006, Paris, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Hernandez-Rapp
authors.affiliation: INRA, UMR1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Castille
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Urien
authors.affiliation: INRA, UMR1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.|INRA, Plateforme MIMA2, Jouy-en-Josas, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chat
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
authors.affiliation: INRA, UMR1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
authors.affiliation: INSERM UMR-S1124, Université Paris Descartes 75006, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Mouillet-Richard
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D002923:Cilia / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D018621:PrPC Proteins / Q000172:deficiency / Q000235:genetics; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D018621:PrPC Proteins; D011328:Prions; D012333:RNA, Messenger; D014404:Tubulin