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J Biol Chem. 2015 Oct 16;290(42):25571-8. doi: 10.1074/jbc.M115.676247. Epub 2015 Sep 1.

The Social Amoeba Dictyostelium discoideum Is Highly Resistant to Polyglutamine Aggregation.

Author information

1
From the Departments of Biochemistry and the Neuroscience Research Center, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226 and.
2
the Neuroscience Research Center, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226 and Cell Biology, Neurobiology, and Anatomy and.
3
From the Departments of Biochemistry and the Neuroscience Research Center, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226 and the Department of Computational and Physical Sciences, Carroll University, Waukesha, Wisconsin 53186.
4
From the Departments of Biochemistry and the Neuroscience Research Center, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226 and mscaglione@mcw.edu.

Abstract

The expression, misfolding, and aggregation of long repetitive amino acid tracts are a major contributing factor in a number of neurodegenerative diseases, including C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia, fragile X tremor ataxia syndrome, myotonic dystrophy type 1, spinocerebellar ataxia type 8, and the nine polyglutamine diseases. Protein aggregation is a hallmark of each of these diseases. In model organisms, including yeast, worms, flies, mice, rats, and human cells, expression of proteins with the long repetitive amino acid tracts associated with these diseases recapitulates the protein aggregation that occurs in human disease. Here we show that the model organism Dictyostelium discoideum has evolved to normally encode long polyglutamine tracts and express these proteins in a soluble form. We also show that Dictyostelium has the capacity to suppress aggregation of a polyglutamine-expanded Huntingtin construct that aggregates in other model organisms tested. Together, these data identify Dictyostelium as a novel model organism with the capacity to suppress aggregation of proteins with long polyglutamine tracts.

KEYWORDS:

Dictyostelium; neurodegenerative disease; polyglutamine; protein aggregation; protein folding

PMID:
26330554
PMCID:
PMC4646202
DOI:
10.1074/jbc.M115.676247
[Indexed for MEDLINE]
Free PMC Article

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