Mutant human FUS is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells

Acosta, Jamie Rae, Goldsbury, Claire, Winnick, Claire, Badrock, Andrew P., Fraser, Stuart T., Laird, Angela S., Hall, Thomas E., Don, Emily K., Fifita, Jennifer A., Blair, Ian P., Nicholson, Garth A. and Cole, Nicholas J. (2014) Mutant human FUS is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells. PLoS One, 9 6: e90572.1-e90572.9. doi:10.1371/journal.pone.0090572


Author Acosta, Jamie Rae
Goldsbury, Claire
Winnick, Claire
Badrock, Andrew P.
Fraser, Stuart T.
Laird, Angela S.
Hall, Thomas E.
Don, Emily K.
Fifita, Jennifer A.
Blair, Ian P.
Nicholson, Garth A.
Cole, Nicholas J.
Title Mutant human FUS is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-06-09
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pone.0090572
Open Access Status DOI
Volume 9
Issue 6
Start page e90572.1
End page e90572.9
Total pages 9
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2015
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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