| RRC ID |
57185
|
| 著者 |
Yamamoto I, Azuma Y, Kushimura Y, Yoshida H, Mizuta I, Mizuno T, Ueyama M, Nagai Y, Tokuda T, Yamaguchi M.
|
| タイトル |
NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Fused in sarcoma (FUS) was identified as a component of typical inclusions in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In FTLD, both nuclear and cytoplasmic inclusions with wild-type FUS exist, while cytoplasmic inclusions with a mutant-form of FUS occur in many ALS cases. These observations imply that FUS plays a role across these two diseases. In this study, we examined the effect of several proteins including molecular chaperons on the aberrant eye morphology phenotype induced by overexpression of wild-type human FUS (hFUS) in Drosophila eye imaginal discs. By screening, we found that the co-expression of nucleophosmin-human myeloid leukemia factor 1 (NPM-hMLF1) fusion protein could suppress the aberrant eye morphology phenotype induced by hFUS. The driving of hFUS expression at 28 °C down-regulated levels of hFUS and endogenous cabeza, a Drosophila homolog of hFUS. The down-regulation was mediated by proteasome dependent degradation. Co-expression of NPM-hMLF1 suppressed this down-regulation. In addition, co-expression of NPM-hMLF1 partially rescued pharate adult lethal phenotype induced by hFUS in motor neurons. These findings with a Drosophila model that mimics FTLD provide clues for the development of novel FTLD therapies.
|
| 巻・号 |
8(1)
|
| ページ |
11291
|
| 公開日 |
2018-7-26
|
| DOI |
10.1038/s41598-018-29716-9
|
| PII |
10.1038/s41598-018-29716-9
|
| PMID |
30050143
|
| PMC |
PMC6062494
|
| MeSH |
Animals
Animals, Genetically Modified*
Cell Cycle Proteins
DNA-Binding Proteins
Disease Models, Animal
Down-Regulation / radiation effects
Drosophila
Eye / embryology
Eye Abnormalities / prevention & control
Frontotemporal Lobar Degeneration / pathology*
Gene Expression*
Humans
Imaginal Discs / embryology
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Nucleophosmin
Proteins / genetics
Proteins / metabolism*
RNA-Binding Protein FUS / genetics
RNA-Binding Protein FUS / metabolism*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism*
Temperature
|
| IF |
4.011
|
| 引用数 |
1
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| リソース情報 |
| ショウジョウバエ |
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