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Lipid rafts and clathrin cooperate in the internalization of PrP in epithelial FRT cells.

Abstract : The cellular prion protein (PrP(C)) plays a key role in the pathogenesis of Transmissible Spongiform Encephalopathies in which the protein undergoes post-translational conversion to the infectious form (PrP(Sc)). Although endocytosis appears to be required for this conversion, the mechanism of PrP(C) internalization is still debated, as caveolae/raft- and clathrin-dependent processes have all been reported to be involved. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the mechanism of PrP(C) endocytosis in Fischer Rat Thyroid (FRT) cells, which lack caveolin-1 (cav-1) and caveolae, and in FRT/cav-1 cells which form functional caveolae. We show that PrP(C) internalization requires activated Cdc-42 and is sensitive to cholesterol depletion but not to cav-1 expression suggesting a role for rafts but not for caveolae in PrP(C) endocytosis. PrP(C) internalization is also affected by knock down of clathrin and by the expression of dominant negative Eps15 and Dynamin 2 mutants, indicating the involvement of a clathrin-dependent pathway. Notably, PrP(C) co-immunoprecipitates with clathrin and remains associated with detergent-insoluble microdomains during internalization thus indicating that PrP(C) can enter the cell via multiple pathways and that rafts and clathrin cooperate in its internalization. CONCLUSIONS/SIGNIFICANCE: These findings are of particular interest if we consider that the internalization route/s undertaken by PrP(C) can be crucial for the ability of different prion strains to infect and to replicate in different cell lines.
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Contributor : Marie Lemesle Connect in order to contact the contributor
Submitted on : Tuesday, June 23, 2009 - 3:16:36 PM
Last modification on : Friday, November 25, 2022 - 6:50:05 PM
Long-term archiving on: : Tuesday, June 15, 2010 - 5:46:05 PM


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Daniela Sarnataro, Anna Caputo, Philippe Casanova, Claudia Puri, Simona Paladino, et al.. Lipid rafts and clathrin cooperate in the internalization of PrP in epithelial FRT cells.. PLoS ONE, 2009, 4 ((6)), pp.e5829. ⟨10.1371/journal.pone.0005829⟩. ⟨pasteur-00396868⟩



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