Title

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

RIS ID

114177

Publication Details

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, Online First 1-10.

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.

Grant Number

NHMRC/108414

Grant Number

NHMRC/1095215

Please refer to publisher version or contact your library.

Share

COinS