Reference - Detail
| RRC ID | 57185 |
|---|---|
| Author | Yamamoto I, Azuma Y, Kushimura Y, Yoshida H, Mizuta I, Mizuno T, Ueyama M, Nagai Y, Tokuda T, Yamaguchi M. |
| Title | NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene. |
| Journal | 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. |
| Volume | 8(1) |
| Pages | 11291 |
| Published | 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 |
| Times Cited | 1 |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | |