FUS/TLS forms cytoplasmic aggregates, inhibits cell growth and interacts with TDP-43 in a yeast model of amyotrophic lateral sclerosis.
10.1007/s13238-011-1525-0
- Author:
Dmitry KRYNDUSHKIN
1
;
Reed B WICKNER
;
Frank SHEWMAKER
Author Information
1. Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
- Publication Type:Journal Article
- MeSH:
Amyotrophic Lateral Sclerosis;
metabolism;
pathology;
Cell Proliferation;
drug effects;
Cytoplasm;
drug effects;
metabolism;
DNA-Binding Proteins;
genetics;
metabolism;
Detergents;
pharmacology;
Humans;
Kinetics;
Peptides;
metabolism;
Prions;
chemistry;
metabolism;
Protein Binding;
drug effects;
Protein Multimerization;
drug effects;
Protein Structure, Quaternary;
Protein Transport;
RNA-Binding Protein FUS;
chemistry;
genetics;
metabolism;
Saccharomyces cerevisiae;
cytology;
drug effects;
genetics;
metabolism;
Saccharomyces cerevisiae Proteins;
chemistry;
metabolism
- From:
Protein & Cell
2011;2(3):223-236
- CountryChina
- Language:English
-
Abstract:
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the premature loss of motor neurons. While the underlying cellular mechanisms of neuron degeneration are unknown, the cytoplasmic aggregation of several proteins is associated with sporadic and familial forms of the disease. Both wild-type and mutant forms of the RNA-binding proteins FUS and TDP-43 accumulate in cytoplasmic inclusions in the neurons of ALS patients. It is not known if these so-called proteinopathies are due to a loss of function or a gain of toxicity resulting from the formation of cytoplasmic aggregates. Here we present a model of FUS toxicity using the yeast Saccharomyces cerevisiae in which toxicity is associated with greater expression and accumulation of FUS in cytoplasmic aggregates. We find that FUS and TDP-43 have a high propensity for co-aggregation, unlike the aggregation patterns of several other aggregation-prone proteins. Moreover, the biophysical properties of FUS aggregates in yeast are distinctly different from many amyloidogenic proteins, suggesting they are not composed of amyloid.
