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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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Hauptverfasser: Streit, Lisa (VerfasserIn) , Kuhn, Timo (VerfasserIn) , Vomhof, Thomas (VerfasserIn) , Bopp, Verena (VerfasserIn) , Ludolph, Albert C. (VerfasserIn) , Weishaupt, Jochen H. (VerfasserIn) , Gebhardt, J. Christof M. (VerfasserIn) , Michaelis, Jens (VerfasserIn) , Danzer, Karin M. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 19 September 2022
In: Nature Communications
Year: 2022, Jahrgang: 13, Pages: 1-18
ISSN:2041-1723
DOI:10.1038/s41467-022-32939-0
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-022-32939-0
Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41467-022-32939-0
Volltext
Verfasserangaben:Lisa Streit, Timo Kuhn, Thomas Vomhof, Verena Bopp, Albert C. Ludolph, Jochen H. Weishaupt, J. Christof M. Gebhardt, Jens Michaelis and Karin M. Danzer
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 10.10.2023
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-022-32939-0

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