Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells.
Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells.
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DOI：
10.1371/journal.pone.0090572
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cole NJ
中科院分区：
文献类型：
--
作者：
Acosta JR;Goldsbury C;Winnick C;Badrock AP;Fraser ST;Laird AS;Hall TE;Don EK;Fifita JA;Blair IP;Nicholson GA;Cole NJ
FUS突变可发生在家族性肌萎缩性侧索硬化症（fALS）中，这是一种运动神经元细胞质FUS包涵体的神经退行性疾病。为了研究FUS病理，我们培育了表达gfp标记的野生型或fALS （R521C）人类FUS的转基因斑马鱼。用这些斑马鱼进行细胞培养，并在不同类型的细胞（包括分化的运动神经元）中检测人类FUS的亚细胞定位和应激颗粒（SG）包涵体的产生。我们证明突变的FUS在运动神经元和所有其他细胞类型中从细胞核到细胞质的错位程度相似。野生型和R521C FUS在斑马鱼细胞中都定位于SGs，表明无论是否存在疾病相关突变或特定细胞类型，人类FUS都具有在SGs中积累的内在能力。然而，R521C突变导致相对胞质到核FUS的升高，导致易感细胞亚群中SG的组装和持久性显著增加，尽管这些细胞不是选择性运动神经元。
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.
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影响因子：
4.2
作者：
Gal J;Zhang J;Kwinter DM;Zhai J;Jia H;Jia J;Zhu H
通讯作者：
Zhu H
DOI：
10.1083/jcb.201302044
发表时间：
2013-04-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Li YR;King OD;Shorter J;Gitler AD
通讯作者：
Gitler AD
影响因子：
56.9
作者：
Kwiatkowski, T. J., Jr.;Bosco, D. A.;Brown, R. H., Jr.
通讯作者：
Brown, R. H., Jr.
影响因子：
3.5
作者：
Armstrong, Gary A. B.;Drapeau, Pierre
通讯作者：
Drapeau, Pierre
影响因子：
4.5
作者：
Huang C;Zhou H;Tong J;Chen H;Liu YJ;Wang D;Wei X;Xia XG
通讯作者：
Xia XG