TY - JOUR
T1 - Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies
AU - Schipper-Krom, S.
AU - Juenemann, K.
AU - Jansen, A.H.
AU - Wiemhoefer, A.
AU - van den Nieuwendijk, R.
AU - Smith, D.L.
AU - Hink, M.A.
AU - Bates, G.P.
AU - Overkleeft, H.
AU - Ovaa, H.
AU - Reits, E.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - https://doi.org/10.1016/j.febslet.2013.11.023
DO - https://doi.org/10.1016/j.febslet.2013.11.023
M3 - Article
C2 - 24291262
SN - 0014-5793
VL - 588
SP - 151
EP - 159
JO - FEBS letters
JF - FEBS letters
IS - 1
ER -