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Updated: Feb 19, 2026

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
Novel amplification mechanism of prions through disrupting sortilin-mediated trafficking
Suehiro Sakaguchi1, Keiji Uchiyama1
1a Division of Molecular Neurobiology, Institute for Enzyme Research (KOSOKEN), Tokushima University , Tokushima , Japan.
Abstract:
Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform of prion protein, PrPSc, which leads to marked accumulation of PrPSc in brains, is a key pathogenic event in prion diseases, a group of fatal neurodegenerative disorders caused by prions. However, the exact mechanism of PrPSc accumulation in prion-infected neurons remains unknown. We recently reported a novel cellular mechanism to support PrPSc accumulation in prion-infected neurons, in which PrPSc itself promotes its accumulation by evading the cellular inhibitory mechanism, which is newly identified in our recent study. We showed that the VPS10P sorting receptor sortilin negatively regulates PrPSc accumulation in prion-infected neurons, by interacting with PrPC and PrPSc and trafficking them to lysosomes for degradation. However, PrPSc stimulated lysosomal degradation of sortilin, disrupting the sortilin-mediated degradation of PrPC and PrPSc and eventually evoking further accumulation of PrPSc in prion-infected neurons. These findings suggest a positive feedback amplification mechanism for PrPSc accumulation in prion-infected neurons.
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