Mutant FUS induces endoplasmic reticulum stress in amyotrophic lateral sclerosis and interacts with protein disulfide-isomerase
Manal A Farg, Kai Y Soo, Adam K Walker, Hong Pham, Jacqueline Orian, Malcolm K Horne, Sadaf T Warraich, Kelly L Williams, Ian P Blair, Julie D Atkin
NEUROBIOLOGY OF AGING | ELSEVIER SCIENCE INC | Published : 2012
Mutations in the gene encoding fused in sarcoma (FUS) are linked to amyotrophic lateral sclerosis (ALS), but the mechanisms by which these mutants trigger neurodegeneration remain unknown. Endoplasmic reticulum (ER) stress is increasingly recognized as an important and early pathway to motor neuron death in ALS. FUS is normally located in the nucleus but in ALS, FUS redistributes to the cytoplasm and forms inclusions. In this study, we investigated whether FUS induces ER stress in a motor neuron like cell line (NSC-34). We demonstrate that ER stress is triggered in cells expressing mutant FUS, and this is closely associated with redistribution of mutant FUS to the cytoplasm. Mutant FUS also ..View full abstract
Awarded by National Health and Medical Research Council of Australia
This work was supported by funding from National Health and Medical Research Council of Australia (project grants 454749 and 570957); MND Research Institute of Australia; Bethlehem Griffiths Research Council, Henry H. Roth Charitable Foundation Grant for MND Research; and Australian Rotary Health.