Cytoplasmic localization of amyotrophic lateral sclerosis‐related TDP‐43 proteins modulates stress granule formation

2020 ◽  
Vol 52 (8) ◽  
pp. 3995-4008 ◽  
Author(s):  
Corinne Besnard‐Guérin
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Stress Granule ◽  
Cytoplasmic Localization ◽  
Granule Formation ◽  
Lateral Sclerosis

scholarly journals Poly(GR) impairs protein translation and stress granule dynamics in C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

2018 ◽  
Vol 24 (8) ◽  
pp. 1136-1142 ◽  
Author(s):  
Yong-Jie Zhang ◽  
Tania F. Gendron ◽  
Mark T. W. Ebbert ◽  
Aliesha D. O’Raw ◽  
Mei Yue ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Frontotemporal Dementia ◽  
Protein Translation ◽  
Stress Granule ◽  
Lateral Sclerosis

scholarly journals Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1367
Author(s):  
Nikita Fernandes ◽  
Luke Nero ◽  
Shawn M. Lyons ◽  
Pavel Ivanov ◽  
Telsa M. Mittelmeier ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Low Dose ◽  
Dna Binding Protein ◽  
Protein Abundance ◽  
Cytoplasmic Localization ◽  
P Bodies ◽  
Aggregation Behaviors ◽  
Protein Granules ◽  
Mutant Cells ◽  
Lateral Sclerosis

Stress granules (SGs) are hypothesized to facilitate TAR DNA-binding protein 43 (TDP-43) cytoplasmic mislocalization and aggregation, which may underly amyotrophic lateral sclerosis pathology. However, much data for this hypothesis is indirect. Additionally, whether P-bodies (PBs; related mRNA-protein granules) affect TDP-43 phenotypes is unclear. Here, we determine that induction of TDP-43 expression in yeast results in the accumulation of SG-like foci that in >90% of cases become the sites where TDP-43 cytoplasmic foci first appear. Later, TDP-43 foci associate less with SGs and more with PBs, though independent TDP-43 foci also accumulate. However, depleting or over-expressing yeast SG and PB proteins reveals no consistent trend between SG or PB assembly and TDP-43 foci formation, toxicity or protein abundance. In human cells, immunostaining endogenous TDP-43 with different TDP-43 antibodies reveals distinct localization and aggregation behaviors. Following acute arsenite stress, all phospho-TDP-43 foci colocalize with SGs. Interestingly, in SG assembly mutant cells (G3BP1/2ΔΔ), TDP-43 is enriched in nucleoli. Finally, formation of TDP-43 cytoplasmic foci following low-dose chronic arsenite stress is impaired, but not completely blocked, in G3BP1/2ΔΔ cells. Collectively, our data suggest that SG and PB assembly may facilitate TDP-43 cytoplasmic localization and aggregation but are likely not essential for these events.

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