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
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
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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.