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标题：Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function
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作者：Ye-Jin Park ; Sungkyung Kim ; Hyeon-Pyo Shim 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：8
页码：1-25
DOI：10.1016/j.isci.2021.102899
语种：English
出版社：Elsevier
摘要：SummaryPhosphatidylserine (PS) is an integral component of eukaryotic cell membranes and organelles. TheDrosophilagenome contains a single PS synthase (PSS)-encoding gene (Pss) homologous to mammalian PSSs. Flies withPssloss-of-function alleles show a reduced life span, increased bang sensitivity, locomotor defects, and vacuolated brain, which are the signs associated with neurodegeneration. We observed defective mitochondria in mutant adult brain, as well as elevated production of reactive oxygen species, and an increase in autophagy and apoptotic cell death. Intriguingly, glial-specific knockdown or overexpression ofPssalters synaptogenesis and axonal growth in the larval stage, causes developmental arrest in pupal stages, and neurodegeneration in adults. This is not observed with pan-neuronal up- or down-regulation. These findings suggest that precisely regulated expression ofPssin glia is essential for the development and maintenance of brain function. We propose a mechanism that underlies these neurodegenerative phenotypes triggered by defective PS metabolism.Graphical abstractDisplay OmittedHighlights•Loss ofPssleads to developmental defects and neurodegeneration•Loss ofPsscauses a mitochondrial defect, elevated ROS, and secondary necrosis•Pssfunctions in glia are essential for synaptogenesis and neuronal maintenance•GlialPssexpression level must be tightly regulated to maintain a healthy nervous systemDevelopmental neuroscience; Cell biology; Developmental biology