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NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene.


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.

SUBMITTER: Yamamoto I 

PROVIDER: S-EPMC6062494 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene.

Yamamoto Itaru I   Azuma Yumiko Y   Kushimura Yukie Y   Yoshida Hideki H   Mizuta Ikuko I   Mizuno Toshiki T   Ueyama Morio M   Nagai Yoshitaka Y   Tokuda Takahiko T   Yamaguchi Masamitsu M  

Scientific reports 20180726 1


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 mor  ...[more]

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