The ataxin-1 interactome reveals direct connection with multiple disrupted nuclear transport pathways
| Autor: | Marie A. Bogoyevitch, Yee-Foong Mok, Praseuth Yang, Lisa A. Duvick, Nicholas A. Williamson, Alexander Lee, David A. Jans, Harry T. Orr, Austin Korlin-Downs, Sunyuan Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Spinocerebellar Ataxia Type 1 Nucleocytoplasmic Transport Proteins congenital hereditary and neonatal diseases and abnormalities Science Active Transport Cell Nucleus General Physics and Astronomy Ataxin 1 General Biochemistry Genetics and Molecular Biology Nucleoporin 62 Article 03 medical and health sciences Mice Purkinje Cells 0302 clinical medicine Cell Line Tumor medicine Animals Humans Spinocerebellar Ataxias Nuclear protein lcsh:Science Ataxin-1 Cell Nucleus Multidisciplinary biology General Chemistry medicine.disease Cell biology Protein-protein interaction networks Nuclear Pore Complex Proteins Cell nucleus Disease Models Animal 030104 developmental biology medicine.anatomical_structure Mutation Nuclear transport biology.protein Spinocerebellar ataxia lcsh:Q Peptides Trinucleotide Repeat Expansion 030217 neurology & neurosurgery HeLa Cells Protein Binding |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The expanded polyglutamine (polyQ) tract form of ataxin-1 drives disease progression in spinocerebellar ataxia type 1 (SCA1). Although known to form distinctive intranuclear bodies, the cellular pathways and processes that polyQ-ataxin-1 influences remain poorly understood. Here we identify the direct and proximal partners constituting the interactome of ataxin-1[85Q] in Neuro-2a cells, pathways analyses indicating a significant enrichment of essential nuclear transporters, pointing to disruptions in nuclear transport processes in the presence of elevated levels of ataxin-1. Our direct assessments of nuclear transporters and their cargoes confirm these observations, revealing disrupted trafficking often with relocalisation of transporters and/or cargoes to ataxin-1[85Q] nuclear bodies. Analogous changes in importin-β1, nucleoporin 98 and nucleoporin 62 nuclear rim staining are observed in Purkinje cells of ATXN1[82Q] mice. The results highlight a disruption of multiple essential nuclear protein trafficking pathways by polyQ-ataxin-1, a key contribution to furthering understanding of pathogenic mechanisms initiated by polyQ tract proteins. Patients with spinocerebellar ataxia type 1 express ataxin-1 with an extended polyglutamine (polyQ) tract that forms distinctive nuclear bodies. Here, the authors characterize the cellular pathways affected by polyQ-ataxin-1, showing that it disrupts multiple nuclear transport processes. |
| Databáze: | OpenAIRE |
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