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dc.contributor.authorXiao, Chengfeng
dc.contributor.authorQiu, Shuang
dc.contributor.authorLi, Xiao
dc.contributor.authorLuo, Dan-Ju
dc.contributor.authorLiu, Gong-Ping
dc.identifier.citationXiao, C., Qiu, S., Li, X., Luo, D.-J., & Liu, G.-P. (2019). EDTP/MTMR14: A novel target for improved survivorship to prolonged anoxia and cellular protein aggregates. Neuroscience Letters, 705, 151–158. doi:10.1016/j.neulet.2019.04.053en
dc.descriptionThe final publication is available at Elsevier via ©2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
dc.description.abstractDrosophila egg-derived tyrosine phosphatase (EDTP), a lipid phosphatase that removes 3-position phosphate at the inositol ring, has dual functions in oogenesis and muscle performance in adults. A mammalian homologous gene MTMR14, which encodes the myotubularin-related protein 14, negatively regulates autophagy. Mutation of EDTP/MTMR14, however, causes at least three deleterious consequences: (1) the lethality in early embryogenesis in Drosophila; (2) a “jumpy” phenotype with apparently impaired motor functions; and (3) an association with a rare genetic disorder called centronuclear myopathy. The potential benefit of EDTP/MTMR14 downregulation is likely masked by the lethality or severe muscle defects due to ubiquitous loss of this gene. Here we show that flies carrying a heterozygous EDTP mutation had increased survivorship to prolonged anoxia; tissue-specific downregulation of EDTP in non-muscle tissues, particularly motoneurons, extended lifespan and improved survivorship to beta-amyloid peptides (Aβ42) and polyglutamine protein aggregates. These data highlight the significance of selective downregulation of EDTP in non-muscles for beneficial consequences. MTMR14 expression was evident in the hippocampus and cortex in C57BL/6 J and APP/PS1 mice. Compared with C57BL/6 J mice, APP/PS1 mice had reduced MTMR14 in the cortex. Hippocampal expression of MTMR14 was increased and plateaued at 9–17 months compared with 2–6 months in C57BL/6 J mice. Additionally, MTMR14 was inducible by Aβ42 in the rat primarily hippocampal neurons and mouse Neuro2a neuroblasts. We demonstrate a novel approach of tissue-specific downregulation of the disease-associated gene EDTP/MTMR14 for extended lifespan and improved survivorship to cellular protein aggregates. This approach could be extended from insects to mammals.en
dc.description.sponsorshipFundamental Research Funds for the Central Universities: 30918011308en
dc.description.sponsorshipNational Natural Science Foundation of China: 81501211en
dc.description.sponsorshipNatural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province: BK20180497en
dc.description.sponsorshipJiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse of Nanjing University of Science and Technology: 30918014102en
dc.subjectBeta-amyloid peptideen
dc.subjectEgg-derived tyrosine phosphataseen
dc.subjectMyotubularin-related protein 14en
dc.subjectPolyglutamine protein aggregateen
dc.subjectTissue-specific expressionen
dc.titleEDTP/MTMR14: A novel target for improved survivorship to prolonged anoxia and cellular protein aggregatesen
dc.typejournal articleen

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