Journal article

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

Sunyuan Zhang, Nicholas A Williamson, Lisa Duvick, Alexander Lee, Harry T Orr, Austin Korlin-Downs, Praseuth Yang, Yee-Foong Mok, David A Jans, Marie A Bogoyevitch

Nature Communications | Nature Research | Published : 2020

Abstract

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 traff..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NIH/NINDS


Funding Acknowledgements

This work was funded by a grant (1121907) to M.A.B. and D.A.J. from the Australian National Health and Medical Research Council (NHMRC), and an NIH/NINDS grant to H.T.O. (NS022920-30). S.Z. also acknowledges the scholarship support by the University of Melbourne (Melbourne International Research Scholarship). The mycBioID vector (pcDNA3.1 mycBioID) was a gift from K. Roux (addgene plasmid # 35700), the BiFC vectors were a gift from C.-D. Hu (addgene plasmids #22011, #22013, #22014, # 27097, #27098), and the GFP-ataxin-1[85Q] and GFP-ataxin-1[30Q] plasmids were provided by D.M. Hatters (University of Melbourne). We acknowledge access to the following facilities at the University of Melbourne: the Bio21 Institute Mass Spectrometry and Proteomics Facility, the Macromolecular Interactions Facility, Melbourne Brain Centre (MBC) flow cytometry facility, and the Biological Optical Microscopy Platform. We also acknowledge access to the Monash Micro Imaging Facility at Monash University, Clayton.