| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2048110 | FEBS Letters | 2012 | 6 Pages |
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 α-synuclein (α-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 α-syn and sequestered it in the cytosol. In turn, α-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 interactionsHtt and Httphysically interact by bimolecular fluorescence complementation (View interaction)alpha-syn and Httphysically interact by bimolecular fluorescence complementation (View interaction)alpha-syn and alpha-synphysically interact by comigration in non-denaturing gel electrophoresis (View interaction)Htt and Httphysically interact by comigration in non-denaturing gel electrophoresis (View interaction)alpha-syn and Httcolocalize by fluorescence microscopy (View Interaction: 1, 2)alpha-syn and alpha-synphysically interact by bimolecular fluorescence complementation (View interaction)Htt and alpha-synphysically interact by comigration in non-denaturing gel electrophoresis (View interaction)
► We used BiFC assays to study the interaction between huntingtin and α-synuclein. ► Huntingtin and α-synuclein interact, heterodimerize and co-aggregate. ► Huntingtin modifies α-synuclein intracellular distribution. ► Huntingtin and α-synuclein modify each other’s pattern of aggregation. ► Protein co-aggregation is relevant in many neurodegenerative disorders.
