Oct 25, 2012

Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP

Molecular Neurodegeneration
Anaïs AulasChristine Vande Velde

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, a cell type that is intrinsically more vulnerable than other cell types to exogenous stress. The interplay between genetic susceptibility and environmental exposures to toxins has long been thought to be relevant to ALS. One cellular mechanism to overcome stress is the formation of small dense cytoplasmic domains called stress granules (SG) which contain translationally arrested mRNAs. TDP-43 (encoded by TARDBP) is an ALS-causative gene that we have previously implicated in the regulation of the core stress granule proteins G3BP and TIA-1. TIA-1 and G3BP localize to SG under nearly all stress conditions and are considered essential to SG formation. Here, we report that TDP-43 is required for proper SG dynamics, especially SG assembly as marked by the secondary aggregation of TIA-1. We also show that SG assembly, but not initiation, requires G3BP. Furthermore, G3BP can rescue defective SG assembly in cells depleted of endogenous TDP-43. We also demonstrate that endogenous TDP-43 and FUS do not have overlapping functions in this cellular process as SG initiation and assembly occur normally...Continue Reading

  • References50
  • Citations39

Citations

Mentioned in this Paper

TARDBP gene
Immunofluorescence Assay
Immunoblotting, Reverse
Transfection
Cellular Process
Cytoplasmic mRNA Processing Body
Toxin
TARDBP
G3BP1 gene
Aggregation

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