title: PrPC Undergoes Basal to Apical Transcytosis in Polarized Epithelial MDCK Cells.
abstract: The Prion Protein (PrP) is an ubiquitously expressed glycosylated membrane protein attached to the external leaflet of the plasma membrane via a glycosylphosphatidylinositol anchor (GPI). While the misfolded PrPSc scrapie isoform is the infectious agent of prion disease, the cellular isoform (PrPC) is an enigmatic protein with unclear function. Of interest, PrP localization in polarized MDCK cells is controversial and its mechanism of trafficking is not clear. Here we investigated PrP traffic in MDCK cells polarized on filters and in three-dimensional MDCK cysts, a more physiological model of polarized epithelia. We found that, unlike other GPI-anchored proteins (GPI-APs), PrP undergoes basolateral-to-apical transcytosis in fully polarized MDCK cells. Following this event full-length PrP and its cleavage fragments are segregated in different domains of the plasma membrane in polarized cells in both 2D and 3D cultures.
authors.affiliation: Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25-28 rue du docteur Roux, 75015, Paris, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Arkhipenko
authors.affiliation: Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25-28 rue du docteur Roux, 75015, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Syan
authors.affiliation: Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25-28 rue du docteur Roux, 75015, Paris, France.
authors.forename: Guiliana Soraya
authors.initials: GS
authors.lastname: Victoria
authors.affiliation: Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25-28 rue du docteur Roux, 75015, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lebreton
authors.affiliation: Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25-28 rue du docteur Roux, 75015, Paris, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zurzolo
mesh_terms: D000818:Animals; D019921:Biotinylation; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D004285:Dogs; D000939:Epitopes / Q000737:chemistry; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D012608:Scrapie / Q000378:metabolism; D057900:Transcytosis
chemical_list: D000939:Epitopes; D017261:Glycosylphosphatidylinositols; D018621:PrPC Proteins; D011328:Prions