title: Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD.
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.
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.
authors: Steven
authors: S
authors: Boeynaems
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.
authors: Elke
authors: E
authors: Bogaert
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.
authors: Emiel
authors: E
authors: Michiels
authors: Department of Molecular Genetics, VIB, B-2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, B-2610 Antwerp, Belgium.
authors: Ilse
authors: I
authors: Gijselinck
authors: Department of Molecular Genetics, VIB, B-2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, B-2610 Antwerp, Belgium.|Department of Neurology, University Hospital Ghent and University of Ghent, B-9000 Ghent, Belgium.
authors: Anne
authors: A
authors: Sieben
authors: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 USA.
authors: Ana
authors: A
authors: Jovičić
authors: Switch Laboratory, VIB, B-3000 Leuven, Belgium.|Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium.
authors: Greet
authors: G
authors: De Baets
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.
authors: Wendy
authors: W
authors: Scheveneels
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.
authors: Jolien
authors: J
authors: Steyaert
authors: Department of Molecular Genetics, VIB, B-2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, B-2610 Antwerp, Belgium.
authors: Ivy
authors: I
authors: Cuijt
authors: VIB Laboratory of Systems Biology, Gaston Geenslaan 1, B-3001 Leuven, Belgium.|KU Leuven - University of Leuven, Department of Microbial and Molecular Systems, Laboratory for Genetics and Genomics, Gaston Geenslaan 1, B-3001 Leuven, Belgium.
authors: Kevin J
authors: KJ
authors: Verstrepen
authors: KU Leuven - University of Leuven, Department of Human Genetics, Laboratory of Behavioral and Developmental Genetics, B-3000 Leuven, Belgium.|VIB Center for the Biology of Disease, B-3000 Leuven, Belgium.
authors: Patrick
authors: P
authors: Callaerts
authors: Switch Laboratory, VIB, B-3000 Leuven, Belgium.|Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium.
authors: Frederic
authors: F
authors: Rousseau
authors: Switch Laboratory, VIB, B-3000 Leuven, Belgium.|Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium.
authors: Joost
authors: J
authors: Schymkowitz
authors: Department of Molecular Genetics, VIB, B-2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, B-2610 Antwerp, Belgium.
authors: Marc
authors: M
authors: Cruts
authors: Department of Molecular Genetics, VIB, B-2610 Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, B-2610 Antwerp, Belgium.
authors: Christine
authors: C
authors: Van Broeckhoven
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.|University Hospitals Leuven, Department of Neurology, B-3000 Leuven, Belgium.
authors: Philip
authors: P
authors: Van Damme
authors: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 USA.
authors: Aaron D
authors: AD
authors: Gitler
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.|University Hospitals Leuven, Department of Neurology, B-3000 Leuven, Belgium.
authors: Wim
authors: W
authors: Robberecht
authors: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium.|VIB, Vesalius Research Center, Laboratory of Neurobiology, B-3000 Leuven, Belgium.
authors: Ludo
authors: L
authors: Van Den Bosch
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics*; D005123:Eye / Q000473:pathology; D057180:Frontotemporal Dementia / Q000235:genetics*; D017344:Genes, Insect; D005820:Genetic Testing; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D034622:RNA Interference; D020449:Repetitive Sequences, Amino Acid
chemical_list: D004151:Dipeptides; D001120:Arginine