α-Synuclein modifies huntingtin aggregation in living cells

Several neurodegenerative disorders are characterized by the accumulation of proteinaceous inclusions in the central nervous system. These inclusions are frequently composed of a mixture of aggregation-prone proteins. Here, we used a bimolecular fluorescence complementation assay to study the initial steps of the co-aggregation of huntingtin (Htt) and alpha-synuclein (alpha-syn), two aggregation-prone proteins involved in Huntington's disease (HD) and Parkinson's disease (PD), respectively. We found that Htt (exon 1) oligomerized with alpha-syn and sequestered it in the cytosol. In turn, alpha-syn increased the number of cells displaying aggregates, decreased the number of aggregates per cell and increased the average size of the aggregates. Our results support the idea that co-aggregation of aggregation-prone proteins can contribute to the histopathology of neurodegenerative disorders. Structured summary of protein interactions: Htt and Htt physically interact by bimolecular fluorescence complementation (View interaction) alpha-syn and Htt physically interact by bimolecular fluorescence complementation (View interaction) alpha-syn and alpha-syn physically interact by comigration in non-denaturing gel electrophoresis (View interaction) Htt and Htt physically interact by comigration in non-denaturing gel electrophoresis (View interaction) alpha-syn and Htt colocalize by fluorescence microscopy (View Interaction: 1, 2) alpha-syn and alpha-syn physically interact by bimolecular fluorescence complementation (View interaction) Htt and alpha-syn physically interact by comigration in non-denaturing gel electrophoresis (View interaction) (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.