PUBLICATION

Mutant Human FUS Is Ubiquitously Mislocalized and Generates Persistent Stress Granules in Primary Cultured Transgenic Zebrafish Cells

Authors
Acosta, J.R., Goldsbury, C., Winnick, C., Badrock, A.P., Fraser, S.T., Laird, A.S., Hall, T.E., Don, E.K., Fifita, J.A., Blair, I.P., Nicholson, G.A., Cole, N.J.
ID
ZDB-PUB-140610-2
Date
2014
Source
PLoS One   9(6): e90572 (Journal)
Registered Authors
Badrock, Andrew P., Cole, Nicholas, Don, Emily, Hall, Thomas
Keywords
none
MeSH Terms
  • Animals
  • Cells, Cultured
  • Humans
  • Motor Neurons/cytology
  • Protein Transport/genetics
  • Cytosol/metabolism*
  • RNA-Binding Protein FUS/genetics*
  • RNA-Binding Protein FUS/metabolism*
  • Mutation*
  • Cytoplasmic Granules/metabolism*
  • Zebrafish/genetics*
  • Zebrafish/metabolism*
  • Animals, Genetically Modified
(all 13)
PubMed
24912067 Full text @ PLoS One
Abstract
FUS mutations can occur in familial amyotrophic lateral sclerosis (fALS), a neurodegenerative disease with cytoplasmic FUS inclusion bodies in motor neurons. To investigate FUS pathology, we generated transgenic zebrafish expressing GFP-tagged wild-type or fALS (R521C) human FUS. Cell cultures were made from these zebrafish and the subcellular localization of human FUS and the generation of stress granule (SG) inclusions examined in different cell types, including differentiated motor neurons. We demonstrate that mutant FUS is mislocalized from the nucleus to the cytosol to a similar extent in motor neurons and all other cell types. Both wild-type and R521C FUS localized to SGs in zebrafish cells, demonstrating an intrinsic ability of human FUS to accumulate in SGs irrespective of the presence of disease-associated mutations or specific cell type. However, elevation in relative cytosolic to nuclear FUS by the R521C mutation led to a significant increase in SG assembly and persistence within a sub population of vulnerable cells, although these cells were not selectively motor neurons.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Acosta, J.R., Goldsbury, C., Winnick, C., Badrock, A.P., Fraser, S.T., Laird, A.S., Hall, T.E., Don, E.K., Fifita, J.A., Blair, I.P., Nicholson, G.A., Cole, N.J. (2014) Mutant Human FUS Is Ubiquitously Mislocalized and Generates Persistent Stress Granules in Primary Cultured Transgenic Zebrafish Cells. PLoS One. 9(6):e90572.