Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Yeast Strains and Growth Conditions
2.2. Plasmids
2.3. Yeast Serial Dilution Assays
2.4. Microscopy
2.5. Western Blots
2.6. CRISPR/Cas9-Mediated Knockout of TDP-43
2.7. U-2 OS Cell Culture and Immunohistochemistry
3. Results
3.1. TDP-43 Foci Formation Largely Initiates at SGs in Yeast, Followed by Later PB Localization
3.2. Yeast SG Assembly Mutants Show Minor or No Effect on TDP-43 Toxicity and Foci Formation
3.3. Yeast PB Mutants, with the Exception of edc3Δ pat1Δ, Show No Effect on TDP-43 Foci Formation or Toxicity
3.4. Over-Expression of SG and PB Assembly Proteins Causes Variable Effects on TDP-43 Toxicity, Foci Formation and Protein Abundance
3.5. Endogenous TDP-43 Colocalizes with Mammalian SGs, although Antibodies Utilized Affect Detection
3.6. SG Assembly May Positively Impact Formation of Persistent TDP-43 Cytoplasmic Foci under Chronic but Not Acute Stress
3.7. TDP-43 Protein Levels Decrease Following Stress in SG Assembly Mutant Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Fernandes, N.; Nero, L.; Lyons, S.M.; Ivanov, P.; Mittelmeier, T.M.; Bolger, T.A.; Buchan, J.R. Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation. Biomolecules 2020, 10, 1367. https://doi.org/10.3390/biom10101367
Fernandes N, Nero L, Lyons SM, Ivanov P, Mittelmeier TM, Bolger TA, Buchan JR. Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation. Biomolecules. 2020; 10(10):1367. https://doi.org/10.3390/biom10101367
Chicago/Turabian StyleFernandes, Nikita, Luke Nero, Shawn M. Lyons, Pavel Ivanov, Telsa M. Mittelmeier, Timothy A. Bolger, and J. Ross Buchan. 2020. "Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation" Biomolecules 10, no. 10: 1367. https://doi.org/10.3390/biom10101367