Journal article

Immiscible inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation

Mona Radwan, Jordan D Lilley, Ching-Seng Ang, Gavin E Reid, Danny M Hatters

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2020

Abstract

Poly(glycine-alanine) (polyGA) is one of the polydipeptides expressed in Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 1 caused by C9ORF72 mutations and accumulates as inclusion bodies in the brain of patients. Superficially these inclusions are similar to those formed by polyglutamine (polyQ)-expanded Huntingtin exon 1 (Httex1) in Huntington's disease. Both have been reported to form an amyloid-like structure suggesting they might aggregate via similar mechanisms and therefore recruit the same repertoire of endogenous proteins. When co-expressed in the same cell, polyGA101 and Httex1(Q97) inclusions adopted immiscible phases suggesting different endogenous proteins would be e..

View full abstract

Grants

Awarded by National Health and Medical Research Council


Awarded by Australian Research Council


Funding Acknowledgements

This work was funded by grants to DMH (National Health and Medical Research Council APP1161803 (https://www.nhmrc.gov.au/) and Motor Neuron Disease Research Institute, Australia small grant (https://www.mndaust.asn.au/Discover-our-research/About-MNDRIA.aspx)) and to DMH and GER (Australian Research Council DP170103093) (https://www.arc.gov.au/). MR acknowledges support from an Australian Government Research Training Program (RTP) Scholarship via the University of Melbourne (https://scholarships.unimelb.edu.au/awards/research-training-program-scholarship) and an Egyptian Ministry of Higher Education and Scientific Research PhD scholarship (http://portal.mohesr.gov.eg/en-us/Pages/default.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.