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Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies
Author(s) -
Schipper-Krom Sabine,
Juenemann Katrin,
Jansen Anne H.,
Wiemhoefer Anne,
van den Nieuwendijk Rianne,
Smith Donna L.,
Hink Mark A.,
Bates Gillian P.,
Overkleeft Hermen,
Ovaa Huib,
Reits Eric
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.11.023
Subject(s) - proteasome , inclusion bodies , microbiology and biotechnology , ubiquitin , intracellular , huntington's disease , biology , disease , huntingtin , chemistry , biochemistry , medicine , gene , escherichia coli
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.