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

Ye-Jin Park; Sungkyung Kim; Hyeon-Pyo Shim; Jae H Park; Gyunghee Lee; Tae-Yeop Kim; Min-Cue Jo; Ah-Young Kwon; Mihwa Lee; Seongjae Lee; Jiwon Yeo; Hyung-Lok Chung; Hugo J Bellen; Seung-Hae Kwon; Sang-Hak Jeon

doi:10.1016/j.isci.2021.102899

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

iScience. 2021 Jul 24;24(8):102899. doi: 10.1016/j.isci.2021.102899. eCollection 2021 Aug 20.

Authors

Ye-Jin Park^{1

2}, Sungkyung Kim¹, Hyeon-Pyo Shim³, Jae H Park⁴, Gyunghee Lee⁴, Tae-Yeop Kim¹, Min-Cue Jo¹, Ah-Young Kwon¹, Mihwa Lee¹, Seongjae Lee¹, Jiwon Yeo¹, Hyung-Lok Chung^{2

5

6}, Hugo J Bellen^{2

5

6}, Seung-Hae Kwon⁷, Sang-Hak Jeon¹

Affiliations

¹ Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea.
² Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
³ Korea Institute for Curriculum and Evaluation, Chungcheongbuk-do 27873, Republic of Korea.
⁴ Department of Biochemistry & Cellular and Molecular Biology, and Neuronet Research Center, University of Tennessee, Knoxville 37996, USA.
⁵ Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
⁶ Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
⁷ Korea Basic Science Institute, Seoul Center 02841, Republic of Korea.

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.