| RRC ID |
33636
|
| 著者 |
Acosta JR, Goldsbury C, Winnick C, Badrock AP, Fraser ST, Laird AS, Hall TE, Don EK, Fifita JA, Blair IP, Nicholson GA, Cole NJ.
|
| タイトル |
Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells.
|
| ジャーナル |
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.
|
| 巻・号 |
9(6)
|
| ページ |
e90572
|
| 公開日 |
2014-1-1
|
| DOI |
10.1371/journal.pone.0090572
|
| PII |
PONE-D-13-45008
|
| PMID |
24912067
|
| PMC |
PMC4049593
|
| MeSH |
Animals
Animals, Genetically Modified
Cells, Cultured
Cytoplasmic Granules / metabolism*
Cytosol / metabolism*
Humans
Motor Neurons / cytology
Mutation*
Protein Transport / genetics
RNA-Binding Protein FUS / genetics*
RNA-Binding Protein FUS / metabolism*
Zebrafish / genetics*
Zebrafish / metabolism*
|
| IF |
2.74
|
| 引用数 |
11
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ゼブラフィッシュ |
isl1:GFP/rw0 |
