Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
Scientific Reports2016Vol. 6(1), pp. 20877–20877
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Steven Boeynaems, Elke Bogaert, Emiel Michiels, Ilse Gijselinck, Anne Sieben, Ana Jovičić, Greet De Baets, Wendy Scheveneels, Jolien Steyaert, Ivy Cuijt, Kevin J. Verstrepen, Patrick Callaerts, Frédéric Rousseau, Joost Schymkowitz, Marc Cruts, Christine Van Broeckhoven, Philip Van Damme, Aaron D. Gitler, Wim Robberecht, Ludo Van Den Bosch
Abstract
Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modifier screen in Drosophila and discovered a critical role for importins and exportins, Ran-GTP cycle regulators, nuclear pore components, and arginine methylases in mediating DPR toxicity. These findings provide evidence for an important role for nucleocytoplasmic transport in the pathogenic mechanism of c9ALS/FTD.
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