Steinhauer-Banerjee-TAGC-2020.pdf (7.84 MB)

Calcium independent phospholipase A2-VIA affects female but not male fertility in Drosophila melanogaster, with altered mitochondrial distribution in the developing female germ cells

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posted on 20.04.2020 by Surya Banerjee, Sogol Eizadshenass, Liam Eliach, Shimshon Benji, Yaakov Tzvi Cantor, Matthew Lubin, Jeremy Purow, Adina Schonbrun, Benjamin Shulman, Josefa Steinhauer
iPLA2-VIA, the Drosophila melanogaster homolog of human PLA2G6/PARK14, encodes a calcium independent phospholipase A2 that hydrolyzes glycerophospholipids into free fatty acids and lysophospholipids, thereby regulating membrane phospholipid composition and signaling pathways that can affect neuronal function, fertility, inflammation, metabolism, and apoptosis. Human PLA2G6 mutations are associated with neurodegenerative and locomotor disorders, including inherited dystonia-parkinsonism, in which neuroaxonal dystrophy is correlated with mitochondrial degeneration. However, the underlying mechanisms behind these conditions are not clear. We generated a null mutation in iPLA2-VIA and found that homozygous mutant flies show age-dependent locomotor defects and shortened lifespan, hallmarks of neurodegeneration, as reported in previous studies. Additionally, we observed high expression of iPLA2-VIA transcripts in both the wild-type male and female germlines, and reduced fertility was observed in mutant females. Mutant females laid significantly fewer eggs than controls, and no maternal lethality was seen, suggesting that the reduced fertility results from defects during oogenesis. Wild-type tagged iPLA2-VIA colocalized with a mitochondrial marker in both male and female germlines, and an abnormal distribution of mitochondria in the female germline was observed in the mutant flies. We developed a quantitative method to score this distinct phenotype in mid-oogenesis stage egg chambers. Surprisingly, male fertility as well as many aspects of spermatogenesis were normal in iPLA2-VIA mutants, despite the requirement of the mammalian homolog for male fertility in mice. In summary, reduced female fertility in iPLA2-VIA mutant flies is correlated with mitochondrial defects in the developing female germ cells.

Funding

R15-HD80511-02

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1602C

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