@article{b7a34e779e384905bff7df05b4952118,
title = "Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function",
abstract = "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.",
keywords = "Cell biology, Developmental biology, Developmental neuroscience",
author = "Park, {Ye Jin} and Sungkyung Kim and Shim, {Hyeon Pyo} and Park, {Jae H.} and Gyunghee Lee and Kim, {Tae Yeop} and Jo, {Min Cue} and Kwon, {Ah Young} and Mihwa Lee and Seongjae Lee and Jiwon Yeo and Chung, {Hyung Lok} and Bellen, {Hugo J.} and Kwon, {Seung Hae} and Jeon, {Sang Hak}",
note = "Funding Information: This work was supported by the National Research Foundation of Korea Grant (NRF-2015R1D1A1A01059861, NRF-2019R1F1A1061772) to S.H.J. H.J.B. is an Investigator of the Howard Hughes Medical Institute. H.-L.C. is supported by the Warren Alpert Foundation. We appreciate the technical support of the Korea Basic Science Institute (KBSI), Chuncheon Center, and Seoul Center. Y.-J.P. S.K. H.-P.S. H.-L.C. H.J.B. and S.-H.J. designed the experiments and wrote the manuscript. Y.-J.P. S.K. H.-P.S. T.-Y.K. M.-C.J. M.L, S.L. and J.Y. conducted experiments. A.-Y.K. generated the CRISPR/Cas9 mutation. J.H.P. and G.L. produced the UAS-Pss lines and wrote the manuscript. S.-H.K. conducted the analysis of confocal microscopy images. The authors declare no competing interests. Funding Information: This work was supported by the National Research Foundation of Korea Grant ( NRF-2015R1D1A1A01059861 , NRF-2019R1F1A1061772 ) to S.H.J. H.J.B. is an Investigator of the Howard Hughes Medical Institute . H.-L.C. is supported by the Warren Alpert Foundation . We appreciate the technical support of the Korea Basic Science Institute (KBSI), Chuncheon Center, and Seoul Center. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = aug,
day = "20",
doi = "10.1016/j.isci.2021.102899",
language = "English (US)",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "8",
}