Park Ye-Jin, Kim Sungkyung, Shim Hyeon-Pyo, Park Jae H, Lee Gyunghee, Kim Tae-Yeop, Jo Min-Cue, Kwon Ah-Young, Lee Mihwa, Lee Seongjae, Yeo Jiwon, Chung Hyung-Lok, Bellen Hugo J, Kwon Seung-Hae, Jeon Sang-Hak
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
iScience. 2021 Jul 24;24(8):102899. doi: 10.1016/j.isci.2021.102899. eCollection 2021 Aug 20.
Phosphatidylserine (PS) is an integral component of eukaryotic cell membranes and organelles. The genome contains a single PS synthase (PSS)-encoding gene () homologous to mammalian PSSs. Flies with loss-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 of alters 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 of in 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.
磷脂酰丝氨酸（PS）是真核细胞膜和细胞器的一个组成部分。基因组包含一个与哺乳动物PS合成酶（PSS）同源的单一PS合成酶（PSS）编码基因（）。功能丧失等位基因的果蝇寿命缩短、对惊吓的敏感性增加、运动缺陷以及脑空泡化，这些都是与神经退行性变相关的迹象。我们在突变成年果蝇的大脑中观察到线粒体缺陷，以及活性氧的产生增加，自噬和凋亡性细胞死亡也增加。有趣的是，胶质细胞特异性敲低或过表达会改变幼虫阶段的突触形成和轴突生长，导致蛹期发育停滞，并在成虫中引发神经退行性变。泛神经元上调或下调则未观察到这种情况。这些发现表明，胶质细胞中精确调控的表达对于脑功能的发育和维持至关重要。我们提出了一种机制，该机制是由有缺陷的PS代谢引发的这些神经退行性表型的基础。
