A seeding reaction recapitulates intracellular formation of Sarkosyl-insoluble transactivation response element (TAR) DNA-binding protein-43 inclusions.

ABSTRACT: The transactivation response element (TAR) DNA-binding protein-43 (TDP-43) is a nuclear protein that normally regulates transcription and splicing. Abnormal accumulation of insoluble inclusions containing TDP-43 has been recently reported in the affected tissues of amyotrophic lateral sclerosis (ALS) patients. Here, we show that intracellular aggregation of TDP-43 can be triggered by transduction of fibrillar aggregates prepared from in vitro functional TDP-43. Sarkosyl is found to be incapable of solubilizing those intracellularly seeded aggregates of TDP-43, which is consistent with the observation that TDP-43 inclusions in ALS patients are sarkosyl-insoluble. In addition, intracellular seeding in our cell models reproduces ubiquitination of TDP-43 aggregates, which is another prominent

SUBMITTER: Furukawa Y 

PROVIDER: S-EPMC3099683 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature