Protein & Cell

, Volume 2, Issue 3, pp 223–236

FUS/TLS forms cytoplasmic aggregates, inhibits cell growth and interacts with TDP-43 in a yeast model of amyotrophic lateral sclerosis

Authors

  • Dmitry Kryndushkin
    • Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney DiseasesNational Institutes of Health
    • Department of PharmacologyUniformed Services University of the Health Sciences
  • Reed B. Wickner
    • Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney DiseasesNational Institutes of Health
    • Department of PharmacologyUniformed Services University of the Health Sciences
Research Article

DOI: 10.1007/s13238-011-1525-0

Cite this article as:
Kryndushkin, D., Wickner, R.B. & Shewmaker, F. Protein Cell (2011) 2: 223. doi:10.1007/s13238-011-1525-0

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.

Keywords

amyotrophic lateral sclerosis (ALS)fused in sarcoma (FUS)TLSproteinopathyyeast

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2011