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Updated: Oct 23, 2025

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
Published on: February 5, 2018
Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of
Ye-Jin Park1,2, Sungkyung Kim1, Hyeon-Pyo Shim3
1Department of Science Education/Biology Education, Seoul National University, Seoul 08826, Republic of Korea.
Insights
Phosphatidylserine (PS) is vital for brain health. Its deficiency in Drosophila glia causes neurodegeneration, developmental arrest, and impaired brain function, highlighting PS metabolism
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Phosphatidylserine (PS) is a critical phospholipid in eukaryotic cell membranes.
- The gene encoding phosphatidylserine synthase (PSS) in Drosophila is Pss.
- Loss of Pss function in Drosophila leads to neurodegenerative phenotypes.
Purpose of the Study:
- To investigate the role of Pss in Drosophila brain development and function.
- To elucidate the underlying mechanisms of neurodegeneration caused by Pss deficiency.
Main Methods:
- Utilized Drosophila loss-of-function alleles and glial-specific knockdown/overexpression of Pss.
- Analyzed neurodegenerative phenotypes, including lifespan, behavior, and brain morphology.
- Examined mitochondrial function, reactive oxygen species (ROS) production, autophagy, and apoptosis.
Main Results:
- Pss loss-of-function in Drosophila caused reduced lifespan, locomotor defects, and vacuolated brains.
- Mutant brains exhibited mitochondrial dysfunction, increased ROS, autophagy, and apoptosis.
- Glial-specific Pss manipulation, but not pan-neuronal, resulted in developmental arrest and adult neurodegeneration.
Conclusions:
- Precisely regulated Pss expression in glia is essential for Drosophila brain development and maintenance.
- Defective PS metabolism in glia triggers neurodegenerative phenotypes.
- This study proposes a mechanism for PS metabolism-related neurodegeneration.
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.
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