http://orcid.org/0000-0003-2528-7039
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ABSTRACT
Amyotrophic lateral sclerosis is a devastating neuromuscular degenerative disease characterized by a focal onset of motor neuron loss, followed by contiguous outward spreading of pathology including TAR DNA-binding protein of 43 kDa (TDP-43) aggregates. Previous work suggests that TDP-43 can move between cells. Here we used a novel flow cytometry technique (FloIT) to analyze TDP-43 inclusions and propagation. When cells were transfected to express either mutant G294A TDP-43 fused to GFP or wild type TDP-43fused to tomato red and then co-cultured, flow cytometry detected intact cells containing both fusion proteins and using FloIT detected an increase in the numbers of inclusions in lysates from cells expressing wild type TDP-43-tomato. Furthermore, in this same model, FloIT analyses detected inclusions containing both fusion proteins. These results imply the transfer of TDP-43 fusion proteins between cells and that this process can increase aggregation of wild-type TDP-43 by a mechanism involving co-aggregation with G294A TDP-43.
ABBREVIATIONS
| ALS | = | Amyotrophic Lateral Sclerosis |
| FloIT | = | flow cytometric analysis of inclusions and trafficking |
| FBS | = | Fetal Bovine Serum |
| GFP | = | Green Fluorescent Protein |
| PBS | = | Phosphate Buffered Saline |
| SOD1 | = | Cu/Zn Superoxide Dismutase |
| TDP-43 | = | TAR DNA Binding Protein |
| WT | = | Wild-type |
DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
No potential conflict of interest was reported by the authors.
FUNDING
This work was supported by the NHMRC under Grant 1084144 and 1095215.
