Journal
PROTEIN & CELL
Volume 2, Issue 3, Pages 223-236Publisher
SPRINGEROPEN
DOI: 10.1007/s13238-011-1525-0
Keywords
amyotrophic lateral sclerosis (ALS); fused in sarcoma (FUS); TLS; proteinopathy; yeast
Categories
Funding
- Uniformed Services University of the Health Sciences
- Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available