RRC ID 67566
Author Park YJ, Kim S, Shim HP, Park JH, Lee G, Kim TY, Jo MC, Kwon AY, Lee M, Lee S, Yeo J, Chung HL, Bellen HJ, Kwon SH, Jeon SH.
Title Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function.
Journal iScience
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.
Volume 24(8)
Pages 102899
Published 2021-8-20
DOI 10.1016/j.isci.2021.102899
PII S2589-0042(21)00867-1
PMID 34401677
PMC PMC8358705
IF 4.447
Resource
Drosophila TBX-0002 TBX-0004 TBX-0009 CAS-0001 TBX-0010 DGRC#104172 DGRC#112830 DGRC#105188 DGRC#112853