Stress induced TDP-43 mobility loss independent of stress granules
TAR DNA binding protein 43 (TDP-43) is closely related to the pathogenesis of amyotrophic lateral sclerosis (ALS) and translocates to stress granules (SGs). The role of SGs as aggregation-promoting “crucibles” for TDP-43, however, is still under debate. We analyzed TDP-43 mobility and localization u...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 September 2022
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| In: |
Nature Communications
Year: 2022, Volume: 13, Pages: 1-18 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-022-32939-0 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-022-32939-0 Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41467-022-32939-0 
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| Author Notes: | Lisa Streit, Timo Kuhn, Thomas Vomhof, Verena Bopp, Albert C. Ludolph, Jochen H. Weishaupt, J. Christof M. Gebhardt, Jens Michaelis and Karin M. Danzer |
| Summary: | TAR DNA binding protein 43 (TDP-43) is closely related to the pathogenesis of amyotrophic lateral sclerosis (ALS) and translocates to stress granules (SGs). The role of SGs as aggregation-promoting “crucibles” for TDP-43, however, is still under debate. We analyzed TDP-43 mobility and localization under different stress and recovery conditions using live cell single-molecule tracking and super-resolution microscopy. Besides reduced mobility within SGs, a stress induced decrease of TDP-43 mobility in the cytoplasm and the nucleus was observed. Stress removal led to a recovery of TDP-43 mobility, which strongly depended on the stress duration. ‘Stimulated-emission depletion microscopy’ (STED) and ‘tracking and localization microscopy’ (TALM) revealed not only TDP-43 substructures within stress granules but also numerous patches of slow TDP-43 species throughout the cytoplasm. This work provides insights into the aggregation of TDP-43 in living cells and provide evidence suggesting that TDP-43 oligomerization and aggregation takes place in the cytoplasm separate from SGs. |
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| Item Description: | Gesehen am 10.10.2023 |
| Physical Description: | Online Resource |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-022-32939-0 |