Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function

Phosphatidylserine (PS) is an integral component of eukaryotic cell membranes and organelles. The Drosophila genome contains a single PS synthase (PSS)-encoding gene (Pss) homologous to mammalian PSSs. Flies with Pss loss-of-function alleles show a reduced life span, increased bang sensitivity, loco...

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Published in:iScience 2021-08, Vol.24 (8), p.102899-102899, Article 102899
Main Authors: 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
Format: Article
Language:English
Subjects:
Cell biology
Developmental biology
Developmental neuroscience
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Summary:Phosphatidylserine (PS) is an integral component of eukaryotic cell membranes and organelles. The Drosophila genome contains a single PS synthase (PSS)-encoding gene (Pss) homologous to mammalian PSSs. Flies with Pss 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 Pss 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 Pss 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. [Display omitted] •Loss of Pss leads to developmental defects and neurodegeneration•Loss of Pss causes a mitochondrial defect, elevated ROS, and secondary necrosis•Pss functions in glia are essential for synaptogenesis and neuronal maintenance•Glial Pss expression level must be tightly regulated to maintain a healthy nervous system Developmental neuroscience; Cell biology; Developmental biology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2021.102899