A Drosophila model of FUS-related neurodegeneration reveals genetic interaction between FUS and TDP-43.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder characterized by the loss of motor neurons. Fused in sarcoma/translated in liposarcoma (FUS/TLS) and TAR DNA-binding protein (TDP)-43 are DNA/RNA-binding proteins found to be mutated in sporadic and familial forms of ALS. Ectopic expression of human ALS-causing FUS/TLS mutations in Drosophila caused an accumulation of ubiquitinated proteins, neurodegeneration, larval-crawling defect and early lethality. Mutant FUS/TLS localized to both the cytoplasm and nucleus, whereas wild-type FUS/TLS localized only to the nucleus, suggesting that the cytoplasmic localization of FUS/TLS is required for toxicity. Furthermore, we found that deletion of the nuclear export signal strongly suppressed toxicity, suggesting that cyto

SUBMITTER: Lanson NA 

PROVIDER: S-EPMC4288133 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature