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.

Iscience
|August 17, 2021
PubMed

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.

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