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Nucleolus: A Protein Quality Control Compartment.

Pavani Rekulapally1, S N Suresh1

  • 1Centre for Brain Research, Indian Institute of Science, Bangalore 560012, India.

Trends in Biochemical Sciences
|November 1, 2019
PubMed
Summary
This summary is machine-generated.

The nucleolus acts as a cellular quality control center, refolding damaged proteins within liquid-like condensates. This crucial mechanism, dependent on heat-shock protein 70, is disrupted in neurodegenerative diseases.

Keywords:
chaperone-assisted refoldingliquid–liquid phase separationmembraneless compartmentsneurodegenerationnucleolusnucleophosmin 1

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Neuroscience

Background:

  • The nucleolus is primarily known for ribosome biogenesis.
  • Cellular protein homeostasis relies on intricate quality control mechanisms.
  • Misfolded proteins are implicated in the pathogenesis of neurodegenerative disorders.

Purpose of the Study:

  • To investigate the role of the nucleolus in nuclear protein quality control.
  • To elucidate the mechanism by which the nucleolus regulates misfolded proteins.
  • To determine if this mechanism is affected in neurodegeneration.

Main Methods:

  • Utilized advanced microscopy techniques to observe nucleolar dynamics.
  • Employed biochemical assays to analyze protein refolding within the nucleolus.
  • Investigated the involvement of heat-shock protein 70 (Hsp70) in the process.
  • Examined the integrity of this quality control pathway in models of neurodegeneration.

Main Results:

  • Identified the nucleolus as a non-membrane-bound compartment for nuclear protein quality control.
  • Demonstrated that the nucleolus forms liquid-like protein condensates that facilitate protein refolding.
  • Showcased the essential role of Hsp70 in this nucleolar refolding activity.
  • Found that this liquid-liquid phase separation (LLPS)-mediated quality control is impaired in neurodegenerative conditions.

Conclusions:

  • The nucleolus functions as a critical hub for maintaining nuclear proteostasis.
  • Liquid-liquid phase separation within the nucleolus is a key mechanism for refolding misfolded proteins.
  • Dysregulation of nucleolar protein quality control contributes to neurodegeneration, highlighting a potential therapeutic target.