title: Astrocyte-to-neuron intercellular prion transfer is mediated by cell-cell contact.
abstract: Prion diseases are caused by misfolding of the cellular protein PrP(C) to an infectious conformer, PrP(Sc). Intercellular PrP(Sc) transfer propagates conversion and allows infectivity to move from the periphery to the brain. However, how prions spread between cells of the central nervous system is unclear. Astrocytes are specialized non-neuronal cells within the brain that have a number of functions indispensable for brain homeostasis. Interestingly, they are one of the earliest sites of prion accumulation in the brain. A fundamental question arising from this observation is whether these cells are involved in intercellular prion transfer and thereby disease propagation. Using co-culture systems between primary infected astrocytes and granule neurons or neuronal cell lines, we provide direct evidence that prion-infected astrocytes can disseminate prion to neurons. Though astrocytes are capable of secreting PrP, this is an inefficient method of transferring prion infectivity. Efficient transfer required co-culturing and direct cell contact. Astrocytes form numerous intercellular connections including tunneling nanotubes, containing PrP(Sc), often colocalized with endolysosomal vesicles, which may constitute the major mechanism of transfer. Because of their role in intercellular transfer of prions astrocytes may influence progression of the disease.
authors: Unité Trafic Membranaire et Pathogenèse, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris CEDEX 15, France.
authors: Guiliana Soraya
authors: GS
authors: Victoria
authors: Unité Trafic Membranaire et Pathogenèse, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris CEDEX 15, France.
authors: Alexander
authors: A
authors: Arkhipenko
authors: Unité Trafic Membranaire et Pathogenèse, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris CEDEX 15, France.
authors: Seng
authors: S
authors: Zhu
authors: Unité Trafic Membranaire et Pathogenèse, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris CEDEX 15, France.
authors: Sylvie
authors: S
authors: Syan
authors: Unité Trafic Membranaire et Pathogenèse, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris CEDEX 15, France.
authors: Chiara
authors: C
authors: Zurzolo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport
chemical_list: D018620:PrPSc Proteins