NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene
| Autor: | Itaru Yamamoto, Toshiki Mizuno, Takahiko Tokuda, Ikuko Mizuta, Yukie Kushimura, Hideki Yoshida, Yoshitaka Nagai, Morio Ueyama, Yumiko Azuma, Masamitsu Yamaguchi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytoplasmic inclusion Recombinant Fusion Proteins lcsh:Medicine Down-Regulation Gene Expression Cell Cycle Proteins Biology Eye Article Animals Genetically Modified 03 medical and health sciences Gene expression medicine Animals Humans Eye Abnormalities Amyotrophic lateral sclerosis lcsh:Science Multidisciplinary lcsh:R Temperature Nuclear Proteins Proteins Frontotemporal lobar degeneration medicine.disease Phenotype Fusion protein Cell biology DNA-Binding Proteins Imaginal disc Disease Models Animal 030104 developmental biology Imaginal Discs RNA-Binding Protein FUS lcsh:Q Drosophila Frontotemporal Lobar Degeneration Myeloid leukemia factor 1 Nucleophosmin |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |