Skip to main content
placeholder image

Flow cytometric measurement of the cellular propagation of TDP-43 aggregation

Journal Article


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┬ákDa (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.

Publication Date


  • 2017

Published In


Citation


  • Zeineddine, R., Whiten, D. R., Farrawell, N. E., McAlary, L., Hanspal, M. A., Kumita, J. R., Wilson, M. R. & Yerbury, J. J. (2017). Flow cytometric measurement of the cellular propagation of TDP-43 aggregation. Prion, 11 (3), 195-204.

Scopus Eid


  • 2-s2.0-85019248670

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1071

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 195

End Page


  • 204

Volume


  • 11

Issue


  • 3

Place Of Publication


  • United States

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┬ákDa (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.

Publication Date


  • 2017

Published In


Citation


  • Zeineddine, R., Whiten, D. R., Farrawell, N. E., McAlary, L., Hanspal, M. A., Kumita, J. R., Wilson, M. R. & Yerbury, J. J. (2017). Flow cytometric measurement of the cellular propagation of TDP-43 aggregation. Prion, 11 (3), 195-204.

Scopus Eid


  • 2-s2.0-85019248670

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1071

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 195

End Page


  • 204

Volume


  • 11

Issue


  • 3

Place Of Publication


  • United States