دورية أكاديمية
Hypertonic Stress Causes Cytoplasmic Translocation of Neuronal, but Not Astrocytic, FUS due to Impaired Transportin Function
| العنوان: | Hypertonic Stress Causes Cytoplasmic Translocation of Neuronal, but Not Astrocytic, FUS due to Impaired Transportin Function |
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| المؤلفون: | Hock, Eva-Maria, Maniecka, Zuzanna, Hruska-Plochan, Marian, Reber, Stefan, Laferriere, Florent, Sahadevan, Sonu M. K., Ederle, Helena, Gittings, Lauren, Pelkmans, Lucas, Dupuis, Luc, Lashley, Tammaryn, Ruepp, Marc-David, Dormann, Dorothee, Polymenidou, Magdalini |
| المصدر: | Cell Reports |
| بيانات النشر: | Ludwig-Maximilians-Universität München |
| سنة النشر: | 2018 |
| المجموعة: | Open Access LMU (Ludwig-Maximilians-University Munich) |
| مصطلحات موضوعية: | Munich Cluster for Systems Neurology (SyNergy), ddc:610 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Hock, Eva-Maria; Maniecka, Zuzanna; Hruska-Plochan, Marian; Reber, Stefan; Laferriere, Florent; Sahadevan, Sonu M. K.; Ederle, Helena; Gittings, Lauren; Pelkmans, Lucas; Dupuis, Luc; Lashley, Tammaryn; Ruepp, Marc-David; Dormann, Dorothee und Polymenidou, Magdalini (2018): Hypertonic Stress Causes Cytoplasmic Translocation of Neuronal, but Not Astrocytic, FUS due to Impaired Transportin Function. In: Cell Reports, Bd. 24, Nr. 4: S. 987-1000 [PDF, 5MB]; https://epub.ub.uni-muenchen.de/62997/1/62997.pdfTest; http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-62997-7Test; https://epub.ub.uni-muenchen.de/62997Test/ |
| DOI: | 10.1016/j.celrep.2018.06.094 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2018.06.094Test https://epub.ub.uni-muenchen.de/62997/1/62997.pdfTest https://epub.ub.uni-muenchen.de/62997Test/ http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-62997-7Test |
| رقم الانضمام: | edsbas.4FA6535E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2018.06.094 |
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