| Institution: | 1. Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, The Netherlands;2. Department of Bio-Organic Synthesis, Institute of Chemistry, University of Leiden, Einsteinweg 55, 2333 CC Leiden, The Netherlands;3. Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, Great Maze Pond, SE1 9RT London, United Kingdom;4. Section Molecular Cytology, Swammerdam Institute for Life Sciences, University of Amsterdam, Sciencepark 904, 1090 GE Amsterdam, The Netherlands;5. Department of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands |
| Abstract: | 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. |
