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

by Gitler, Aaron D. , Bogaert, Elke , De Baets, Greet , Van Damme, Philip , Robberecht, Wim , Van Den Bosch, Ludo , Cuijt, Ivy , Callaerts, Patrick , Steyaert, Jolien , Schymkowitz, Joost , Gijselinck, Ilse , Verstrepen, Kevin J. , Jovičić, Ana , Rousseau, Frederic , Michiels, Emiel , Sieben, Anne , Cruts, Marc , Scheveneels, Wendy , Van Broeckhoven, Christine , Boeynaems, Steven

in 631/378/1689/1285 / 692/617/375/1917/1285 / Active Transport, Cell Nucleus - genetics / Amyotrophic lateral sclerosis / Amyotrophic Lateral Sclerosis - genetics / Animals / Arginine / Arginine - metabolism / Cell Nucleus - metabolism / Dipeptides - chemistry / Disease Models, Animal / Drosophila melanogaster - genetics / Eye - pathology / Frontotemporal dementia / Frontotemporal Dementia - genetics / Genes, Insect / Genetic Testing / Guanosine triphosphate / HeLa Cells / Humanities and Social Sciences / Humans / Insects / Methylation / multidisciplinary / Neurodegeneration / Nuclear transport / Repetitive Sequences, Amino Acid / RNA Interference / Science / Toxicity

2016

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

2016

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

2016

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Journal Article

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

Gitler, Aaron D.,

Bogaert, Elke,

De Baets, Greet,

Van Damme, Philip,

Robberecht, Wim,

Van Den Bosch, Ludo,

Cuijt, Ivy,

Callaerts, Patrick,

Steyaert, Jolien,

Schymkowitz, Joost,

Gijselinck, Ilse,

Verstrepen, Kevin J.,

Jovičić, Ana,

Rousseau, Frederic,

Michiels, Emiel,

Sieben, Anne,

Cruts, Marc,

Scheveneels, Wendy,

Van Broeckhoven, Christine,

Boeynaems, Steven

2016

Overview

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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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

631/378/1689/1285

/ 692/617/375/1917/1285

/ Active Transport, Cell Nucleus - genetics

/ Amyotrophic lateral sclerosis

/ Amyotrophic Lateral Sclerosis - genetics

/ Animals

/ Arginine