NR AWCS
AU Campana,V.; Sarnataro,D.; Fasano,C.; Casanova,P.; Paladino,S.; Zurzolo,C.
TI Rafts but not the proteasome are involved in the misfolding of a PrP mutant retained in the endoplasmic reticulum
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-04
PT Konferenz-Poster
AB Inherited prion diseases are neurodegenerative pathologies related to genetic mutations in the prion protein (PrP) gene, which favour the conversion of PrPc into a conformationally altered pathogenic form, PrPsc. The molecular basis of PrPc-PrPsc conversion, the intracellular compartment where it occurs and how this process leads to neurological dysfunction are not yet known. We have studied the intracellular synthesis, degradation and localization of a PrP mutant associated with a genetic form of Creutzfeldt-Jakob disease (CJD), PrPT182A, in transfected FRT cells. PrPT182A is retained in the Endoplasmic Reticulum (ER), is mainly associated with Detergent-Resistant Microdomains (DRMs) and is partially resistant to Proteinase K digestion. Although an untranslocated form of this mutant is polyubiquitinated and undergoes ER-associated degradation, the proteasome is not responsible, suggesting that it does not have a role in the pathogenesis of inherited diseases. On the contrary, impairment of PrPT182A association with DRMs by cholesterol depletion leads to its accumulation in the ER and increases substantially its misfolding. These data support the previous hypothesis that DRMs are important for the correct folding of PrP and suggest that they might have a protective role in pathological scrapie-like conversion of PrP mutants.
AD V. Campana, C. Zurzolo: Dipartimento di Biologia e Patologia Cellulare e Molecolare and CEINGE, Centro di Biotecnologie Avanzate, Università degli Studi di Napoli "Federico II", Napoli, Italy, and Unité Trafic Membranaire et Pathogénèse, Institut Pasteur, 25 rue du Docteur Roux, Paris France; D. Sarnataro, S. Paladino: Dipartimento di Biologia e Patologia Cellulare e Molecolare and CEINGE, Centro di Biotecnologie Avanzate, Università degli Studi di Napoli "Federico II", Napoli, Italy; C. Fasano, P. Casanova: Unité Trafic Membranaire et Pathogénèse, Institut Pasteur, 25 rue du Docteur Roux, Paris France
SP englisch
PO Italien