Hypertonic Stress Causes Cytoplasmic Translocation of Neuronal, but Not Astrocytic, FUS due to Impaired Transportin Function
| Autor: | Dorothee Dormann, Stefan Reber, Luc Dupuis, Helena Ederle, Marian Hruska-Plochan, Eva-Maria Hock, Marc-David Ruepp, Florent Laferrière, Zuzanna Maniecka, Lucas Pelkmans, M K Sonu Sahadevan, Tammaryn Lashley, Lauren M. Gittings, Magdalini Polymenidou |
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| Přispěvatelé: | Dieterle, Stéphane, Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University of Bern, Ludwig Maximilian University [Munich] (LMU), UCL, Institute of Neurology [London], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Universität Bern [Bern], Ludwig-Maximilians-Universität München (LMU), Institute of Neurology [London], King‘s College London, Universität Bern [Bern] (UNIBE), Laferriere, Florent, University of Zurich, Polymenidou, Magdalini |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytoplasm MESH: Hippocampus Cytoplasmic inclusion [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology [SDV]Life Sciences [q-bio] MESH: Neurons Chromosomal translocation RNA-binding protein RNA-binding proteins Hippocampus Mice ALS FTD FUS stress granules nucleocytoplasmic shuttling Transportin protein aggregation MESH: Animals Amyotrophic lateral sclerosis Cerebral Cortex Neurons Chemistry MESH: RNA-Binding Protein FUS Cell biology [SDV] Life Sciences [q-bio] MESH: HEK293 Cells Transportin 1 MESH: Cell Nucleus 610 Medicine & health Genetics and Molecular Biology Karyopherins Transfection General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Stress granule 1300 General Biochemistry Genetics and Molecular Biology MESH: Mice Inbred C57BL medicine Animals Humans MESH: Mice Cell Nucleus MESH: Humans MESH: Cytoplasm MESH: Transfection [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology medicine.disease MESH: Karyopherins MESH: Cerebral Cortex Mice Inbred C57BL MESH: Astrocytes HEK293 Cells 030104 developmental biology Hypertonic Stress Astrocytes General Biochemistry RNA-Binding Protein FUS 11493 Department of Quantitative Biomedicine |
| Zdroj: | Cell Reports Cell Reports, 2018, 24 (4), pp.987-1000.e7. ⟨10.1016/j.celrep.2018.06.094⟩ Cell Reports, Elsevier Inc, 2018, 24 (4), pp.987-1000.e7. ⟨10.1016/j.celrep.2018.06.094⟩ Hock, E-M, Maniecka, Z, Hruska-Plochan, M, Reber, S, Laferrière, F, Sahadevan M K, S, Ederle, H, Gittings, L, Pelkmans, L, Dupuis, L, Lashley, T, Ruepp, M-D, Dormann, D & Polymenidou, M 2018, ' Hypertonic Stress Causes Cytoplasmic Translocation of Neuronal, but Not Astrocytic, FUS due to Impaired Transportin Function ', Cell Reports, vol. 24, no. 4, pp. 987-1000.e7 . https://doi.org/10.1016/j.celrep.2018.06.094 Cell Reports, 24 (4) |
| ISSN: | 2666-3864 2211-1247 |
| DOI: | 10.1016/j.celrep.2018.06.094 |
| Popis: | The primarily nuclear RNA-binding protein FUS (fused in sarcoma) forms pathological cytoplasmic inclusions in a subset of early-onset amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. In response to cellular stress, FUS is recruited to cytoplasmic stress granules, which are hypothesized to act as precursors of pathological inclusions. We monitored the stress-induced nucleocytoplasmic shuttling of endogenous FUS in an ex vivo mouse CNS model and human neural networks. We found that hyperosmolar, but not oxidative, stress induced robust cytoplasmic translocation of neuronal FUS, with transient nuclear clearance and loss of function. Surprisingly, this reaction is independent of stress granule formation and the molecular pathways activated by hyperosmolarity. Instead, it represents a mechanism mediated by cytoplasmic redistribution of Transportin 1/2 and is potentiated by transcriptional inhibition. Importantly, astrocytes, which remain unaffected in ALS/FTD-FUS, are spared from this stress reaction that may signify the initial event in the development of FUS pathology. Cell Reports, 24 (4) ISSN:2666-3864 ISSN:2211-1247 |
| Databáze: | OpenAIRE |
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