Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies

TY - JOUR

T1 - Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies

AU - Schipper-Krom, Sabine

AU - Juenemann, Katrin

AU - Jansen, Anne H.

AU - Wiemhoefer, Anne

AU - Van Den Nieuwendijk, Rianne

AU - Smith, Donna L.

AU - Hink, Mark A.

AU - Bates, Gillian P.

AU - Overkleeft, Hermen

AU - Ovaa, Huib

AU - Reits, Eric

PY - 2014/11/26

Y1 - 2014/11/26

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.

KW - Aggregate

KW - Huntington

KW - Polyglutamine

KW - Proteasome

KW - Ubiquitin

UR - http://www.scopus.com/inward/record.url?scp=84890988864&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2013.11.023

DO - 10.1016/j.febslet.2013.11.023

M3 - Article

AN - SCOPUS:84890988864

SN - 0014-5793

VL - 588

SP - 151

EP - 159

JO - FEBS Letters

JF - FEBS Letters

IS - 1

ER -