| Autor: |
Kushimura, Yukie, Azuma, Yumiko, Mizuta, Ikuko, Muraoka, Yuuka, Kyotani, Akane, Yoshida, Hideki, Tokuda, Takahiko, Mizuno, Toshiki, Yamaguchi, Masamitsu |
| Zdroj: |
NeuroReport; July 2018, Vol. 29 Issue: 10 p856-862, 7p |
| Abstrakt: |
Charcot–Marie–Tooth disease (CMT) is the most common hereditary neuropathy, and more than 80 CMT-causing genes have been identified to date. CMT4J is caused by a loss-of-function mutation in the Factor-Induced-Gene 4(FIG4) gene, the product of which plays important roles in endosome–lysosome homeostasis. We hypothesized that Mammalian sterile 20-like kinase(MST) 1and 2, tumor-suppressor genes, are candidate modifiers of CMT4J. We therefore examined the interaction between dFIG4and Hippo(hpo), Drosophilacounterparts of FIG4 and MSTs, respectively, using the DrosophilaCMT4J model with the knockdown of dFIG4. The loss-of-function allele of hpoimproved the rough eye morphology, locomotive dysfunction accompanied by structural defects in the presynaptic terminals of motoneurons, and the enlargement of lysosomes caused by the knockdown of dFIG4. Therefore, we identified hpoas a modifier of phenotypes induced by the knockdown of dFIG4. These results in Drosophilamay provide an insight into the pathogenesis of CMT4J and contribute toward the development of disease-modifying therapy for CMT. We also identified the regulation of endosome–lysosome homeostasis as a novel probable function of Hippo/MST. |
| Databáze: |
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