Human TDP43 is required for ALS‑related annexin A11 toxicity in Drosophila.

ABSTRACT: Genomics allows identification of genes and mutations associated with amyotrophic lateral sclerosis (ALS). Mutations in annexin A11 (ANXA11) are responsible for ~1% of all familial ALS and fronto-temporal dementia cases. The present study used the fruit fly, Drosophila melanogaster, to assess the mechanism of toxicity of ANXA11 mutants in residues that are conserved in the fly ANXB11 protein, the closest homolog to human ANXA11. In immune fluorescence, lifespan and negative geotaxis assays ANXA11 mutants, while displaying some degree of alteration in localization and function, did not exert any relevant organism toxicity in Drosophila. However, they showed a specific interaction with human TAR DNA-binding protein (TDP43). The present study illustrated that the ANXA11 mutants

SUBMITTER: Barnard J 

PROVIDER: S-EPMC11411402 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature