Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies

FEBS Lett. 2014 Jan 3;588(1):151-9. doi: 10.1016/j.febslet.2013.11.023. Epub 2013 Nov 26.


Neurodegenerative disorders such as Huntington's disease are hallmarked by neuronal intracellular inclusion body formation. Whether proteasomes are irreversibly recruited into inclusion bodies in these protein misfolding disorders is a controversial subject. In addition, it has been proposed that the proteasomes may become clogged by the aggregated protein fragments, leading to impairment of the ubiquitin-proteasome system. Here, we show by fluorescence pulse-chase experiments in living cells that proteasomes are dynamically and reversibly recruited into inclusion bodies. As these recruited proteasomes remain catalytically active and accessible to substrates, our results challenge the concept of proteasome sequestration and impairment in Huntington's disease, and support the reported absence of proteasome impairment in mouse models of Huntington's disease.

Keywords: ABP; Aggregate; C4; FRAP; HD; Huntington; IB; Polyglutamine; Proteasome; UPS; Ub; Ubiquitin; activity-based probe; fluorescence recovery after photobleaching; huntington’s disease; inclusion body; mHtt; mutant huntingtin; polyQ; polyglutamine; tetracysteine; ubiquitin; ubiquitin–proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Brain / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • Inclusion Bodies / genetics
  • Inclusion Bodies / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Microscopy, Confocal
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Peptides / genetics
  • Peptides / metabolism*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding
  • Trinucleotide Repeat Expansion / genetics


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Peptides
  • Green Fluorescent Proteins
  • polyglutamine
  • PSMB4 protein, human
  • Proteasome Endopeptidase Complex