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
Affiliations
Ye-Jin Park
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
Sungkyung Kim
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea
Hyeon-Pyo Shim
Korea Institute for Curriculum and Evaluation, Chungcheongbuk-do 27873, Republic of Korea
Jae H. Park
Department of Biochemistry & Cellular and Molecular Biology, and Neuronet Research Center, University of Tennessee, Knoxville 37996, USA
Gyunghee Lee
Department of Biochemistry & Cellular and Molecular Biology, and Neuronet Research Center, University of Tennessee, Knoxville 37996, USA
Tae-Yeop Kim
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea
Min-Cue Jo
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea
Ah-Young Kwon
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea
Mihwa Lee
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea
Seongjae Lee
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea
Jiwon Yeo
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea
Hyung-Lok Chung
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
Hugo J. Bellen
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
Seung-Hae Kwon
Korea Basic Science Institute, Seoul Center 02841, Republic of Korea
Sang-Hak Jeon
Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea; Corresponding author
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.
