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  • Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD.

Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD.

Scientific reports (2016-02-13)
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, Frederic 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Anti-dimethyl-Arginine Antibody, asymmetric (ASYM24), serum, Upstate®