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bioRxiv · 10.1101/438523

The ataxin-1 interactome reveals direct connection with multiple disrupted nuclear transport pathways

Zhang, S.·Williamson, N. A.·Jans, D. A.·Bogoyevitch, M. A.
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Abstract

The expanded polyglutamine (polyQ) tract form of ataxin-1 drives disease progression in spinocerebellar ataxia type 1 (SCA1). Although polyQ-ataxin-1 is known to form distinctive intranuclear bodies, the cellular pathways and functions it influences remain poorly understood. Here, we identify direct and proximal partners constituting the interactome of ataxin-1[85Q] in Neuro-2a cells. Pathways analyses indicate a significant enrichment of essential nuclear transporters in the interactome, pointing to disruptions in nuclear transport processes in the presence of polyQ-ataxin-1. Our direct assessments of nuclear transporters and their cargoes reinforce these observations, revealing disrupted trafficking often with relocalisation of transporters and/or cargoes to ataxin-1[85Q] nuclear bodies. Strikingly, the nucleoporin Nup98, dependent on its GLFG repeats, is recruited into polyQ-ataxin-1 nuclear bodies. Our results highlight a disruption of multiple essential nuclear protein trafficking pathways by polyQataxin-1, a key contribution to furthering understanding of pathogenic mechanisms initiated by polyQ tract proteins.

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Zhang, S., Williamson, N. A., Jans, D. A., Bogoyevitch, M. A.. 2018-10-08. The ataxin-1 interactome reveals direct connection with multiple disrupted nuclear transport pathways. https://doi.org/10.1101/438523

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