Abstract
Repeat expansions in the C9orf72 gene cause amyotrophic lateral sclerosis and frontotemporal dementia characterized by dipeptide-repeat protein (DPR) inclusions. The toxicity associated with two of these DPRs, poly-GR and poly-PR, has been associated with nucleocytoplasmic transport. To investigate the causal role of poly-GR or poly-PR on active nucleocytoplasmic transport, we measured nuclear import and export in poly-GR or poly-PR expressing Hela cells, neuronal-like SH-SY5Y cells and iPSC-derived motor neurons. Our data strongly indicate that poly-GR and poly-PR do not directly impede active nucleocytoplasmic transport.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus* / drug effects
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Amyotrophic Lateral Sclerosis / metabolism
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Amyotrophic Lateral Sclerosis / pathology
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C9orf72 Protein / genetics
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C9orf72 Protein / metabolism*
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Cell Line, Tumor
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DNA Repeat Expansion
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Dipeptides / genetics
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Dipeptides / metabolism
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Exportin 1 Protein
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Fatty Acids, Unsaturated / pharmacology
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Frontotemporal Dementia / metabolism
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Frontotemporal Dementia / pathology
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Genes, Regulator
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HeLa Cells
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Humans
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Induced Pluripotent Stem Cells / cytology
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Induced Pluripotent Stem Cells / metabolism
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Karyopherins / antagonists & inhibitors
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Karyopherins / genetics
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Microscopy, Fluorescence
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Cytoplasmic and Nuclear / genetics
Substances
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C9orf72 Protein
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Dipeptides
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Fatty Acids, Unsaturated
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Karyopherins
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Receptors, Cytoplasmic and Nuclear
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leptomycin B