Ke Zhang, J Gavin Daigle, Kathleen M Cunningham, Alyssa N Coyne, Kai Ruan, Jonathan C Grima, Kelly E Bowen, Harsh Wadhwa, Peiguo Yang, Frank Rigo, J Paul Taylor, Aaron D Gitler, Jeffrey D Rothstein, Thomas E Lloyd
Defects in nucleocytoplasmic transport have been identified as a key pathogenic event in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mediated by a GGGGCC hexanucleotide repeat expansion in C9ORF72, the most common genetic cause of ALS/FTD. Furthermore, nucleocytoplasmic transport disruption has also been implicated in other neurodegenerative diseases with protein aggregation, suggesting a shared mechanism by which protein stress disrupts nucleocytoplasmic transport. Here, we show that cellular stress disrupts nucleocytoplasmic transport by localizing critical nucleocytoplasmic transport factors into stress granules, RNA/protein complexes that play a crucial role in ALS pathogenesis...
April 2, 2018: Cell