The nucleolus functions as a phase-separated protein quality control compartment

The nuclear proteome is rich in stress-sensitive proteins, which suggests that effective protein quality control mechanisms are in place to ensure conformational maintenance. We investigated the role of the nucleolus in this process. In mammalian tissue culture cells under stress conditions, misfolded proteins entered the granular component (GC) phase of the nucleolus. Transient associations with nucleolar proteins such as NPM1 conferred low mobility to misfolded proteins within the liquid-like GC phase, avoiding irreversible aggregation. Refolding and extraction of proteins from the nucleolus during recovery from stress was Hsp70-dependent. The capacity of the nucleolus to store misfolded proteins was…

• EM
  European Molecular Biology Organization
• M
  Max-Planck-Förderstiftung
• DF
  Deutsche Forschungsgemeinschaft
• ER
  European Research Council

  Awards: FP7 GA ERC-2012-SyG_318987–ToPAG, MolMap 680241