title: Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS.
abstract: C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) produced by unconventional translation of the C9orf72 repeat expansions cause neurodegeneration in cell culture and in animal models. We performed two unbiased screens in Saccharomyces cerevisiae and identified potent modifiers of DPR toxicity, including karyopherins and effectors of Ran-mediated nucleocytoplasmic transport, providing insight into potential disease mechanisms and therapeutic targets.
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors: Ana
authors: A
authors: Jovičić
authors: Salk Institute for Biological Studies, Sanford Consortium for Regenerative Medicine, La Jolla, California, USA.
authors: Jerome
authors: J
authors: Mertens
authors: KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium.|Vlaams Instituut voor Biotechnologie (VIB), Vesalius Research Center, Laboratory of Neurobiology, 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), Leuven, Belgium.|Vlaams Instituut voor Biotechnologie (VIB), Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium.
authors: Elke
authors: E
authors: Bogaert
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.|Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, California, USA.
authors: Noori
authors: N
authors: Chai
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.|Department of Biology, Stanford University, Stanford, California, USA.
authors: Shizuka B
authors: SB
authors: Yamada
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors: Joseph W
authors: JW
authors: Paul
authors: Ludwig Institute for Cancer Research, Departments of Cellular and Molecular Medicine and of Neurosciences, University of California at San Diego, La Jolla, California, USA.
authors: Shuying
authors: S
authors: Sun
authors: Salk Institute for Biological Studies, Sanford Consortium for Regenerative Medicine, La Jolla, California, USA.
authors: Joseph R
authors: JR
authors: Herdy
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.|Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, California, USA.
authors: Gregor
authors: G
authors: Bieri
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.|Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, California, USA.
authors: Nicholas J
authors: NJ
authors: Kramer
authors: Salk Institute for Biological Studies, Sanford Consortium for Regenerative Medicine, La Jolla, California, USA.
authors: Fred H
authors: FH
authors: Gage
authors: KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium.|Vlaams Instituut voor Biotechnologie (VIB), Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium.
authors: Ludo
authors: L
authors: Van Den Bosch
authors: KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium.|Vlaams Instituut voor Biotechnologie (VIB), Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium.|University Hospitals Leuven, Department of Neurology, Leuven, Belgium.
authors: Wim
authors: W
authors: Robberecht
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors: Aaron D
authors: AD
authors: Gitler
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000073885:C9orf72 Protein; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042622:DNA Repeat Expansion / Q000502:physiology*; D004151:Dipeptides / Q000235:genetics / Q000378:metabolism*; D057180:Frontotemporal Dementia / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004151:Dipeptides; D011506:Proteins