PrP-containing aggresomes are cytosolic components of an ER quality control mechanism

Tatyana Dubnikov, Tziona Ben-Gedalya, Robert Reiner, Dominic Hoepfner, Wayne A. Cabral, Joan C. Marini, Ehud Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Limited detoxification capacity often directs aggregation-prone, potentially hazardous, misfolded proteins to be deposited in designated cytosolic compartments known as 'aggresomes'. The roles of aggresomes as cellular quality control centers, and the cellular origin of the deposits contained within these structures, remain to be characterized. Here, we utilized the observation that the prion protein (PrP, also known as PRNP) accumulates in aggresomes following the inhibition of folding chaperones, members of the cyclophilin family, to address these questions. We found that misfolded PrP molecules must pass through the endoplasmic reticulum (ER) in order to be deposited in aggresomes, that the Golgi plays no role in this process and that cytosolic PrP species are not deposited in pre-existing aggresomes. Prior to their deposition in the aggresome, PrP molecules lose the ER localization signal and have to acquire a GPI anchor. Our discoveries indicate that PrP aggresomes are cytosolic overflow deposition centers for the ER quality control mechanisms and highlight the importance of these structures for the maintenance of protein homeostasis within the ER.

Original languageAmerican English
Pages (from-to)3635-3647
Number of pages13
JournalJournal of Cell Science
Issue number19
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016. Published by The Company of Biologists Ltd.


  • Aggresome
  • Endoplasmic reticulum
  • Neurodegeneration
  • Prion protein
  • Protein aggregation


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