Endoplasmic Reticulum Stress Signalling Induces Casein Kinase 1-Dependent Formation of Cytosolic TDP-43 Inclusions in Motor Neuron-Like Cells
| Autor: | Ritchie Williamson, Marcus Rattray, David A. Hicks, Laura L Cross |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
TDP-43 CK1 Cell Survival Cytoplasmic inclusion Biochemistry Cell Line 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Cytosol 0302 clinical medicine mental disorders medicine Humans Motor neuron disease Inclusion Bodies Motor Neurons Original Paper Dose-Response Relationship Drug Casein Kinase I Chemistry Tunicamycin Endoplasmic reticulum nutritional and metabolic diseases General Medicine Motor neuron Endoplasmic Reticulum Stress Anti-Bacterial Agents nervous system diseases Cell biology DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Enzyme Induction Unfolded protein response Phosphorylation Casein kinase 1 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neurochemical Research Hicks, D, Cross, L, Williamson, R & Rattray, M 2019, ' Endoplasmic Reticulum Stress Signalling Induces Casein Kinase 1-Dependent Formation of Cytosolic TDP-43 Inclusions in Motor Neuron-Like Cells. ', Neurochemical research . https://doi.org/10.1007/s11064-019-02832-2 |
| ISSN: | 1573-6903 0364-3190 |
| DOI: | 10.1007/s11064-019-02832-2 |
| Popis: | Motor neuron disease (MND) is a progressive neurodegenerative disease with no effective treatment. One of the principal pathological hallmarks is the deposition of TAR DNA binding protein 43 (TDP-43) in cytoplasmic inclusions. TDP-43 aggregation occurs in both familial and sporadic MND; however, the mechanism of endogenous TDP-43 aggregation in disease is incompletely understood. This study focused on the induction of cytoplasmic accumulation of endogenous TDP-43 in the motor neuronal cell line NSC-34. The endoplasmic reticulum (ER) stressor tunicamycin induced casein kinase 1 (CK1)-dependent cytoplasmic accumulation of endogenous TDP-43 in differentiated NSC-34 cells, as seen by immunocytochemistry. Immunoblotting showed that induction of ER stress had no effect on abundance of TDP-43 or phosphorylated TDP-43 in the NP-40/RIPA soluble fraction. However, there were significant increases in abundance of TDP-43 and phosphorylated TDP-43 in the NP-40/RIPA-insoluble, urea-soluble fraction, including high molecular weight species. In all cases, these increases were lowered by CK1 inhibition. Thus ER stress signalling, as induced by tunicamycin, causes CK1-dependent phosphorylation of TDP-43 and its consequent cytosolic accumulation. Electronic supplementary material The online version of this article (10.1007/s11064-019-02832-2) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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