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Mutations of the Gongpo Gene Encoding a Homolog of Mammalian Phosphatidylserine Synthases Cause Neurodegeneration in Drosophila Melanogaster

35 Pages Posted: 27 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Ye-Jin Park

Ye-Jin Park

Seoul National University - Science Education

Sungkyung Kim

Seoul National University - Science Education

Hyeon-Pyo Shim

Korea Institute for Curriculum and Evaluation

Jae H. Park

University of Tennessee, Knoxville - Department of Biochemistry and Cellular and Molecular Biology

Gyunghee Lee

University of Tennessee, Knoxville - Department of Biochemistry and Cellular and Molecular Biology

Tae-Yeop Kim

Seoul National University - Science Education

Min-Cue Jo

Seoul National University - Science Education

Ah-Young Kwon

Seoul National University - Science Education

Mihwa Lee

Seoul National University - Science Education

Seung-Hae Kwon

Korea Basic Science Institute

Sang-Hak Jeon

Seoul National University - Science Education

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Abstract

Phosphatidylserine (PS) is an integral phospholipid component of eukaryotic cell membranes and organelles. The Drosophila genome contains a single PS synthase-encoding gene (Gongpo, Gong for short) with a protein sequence homologous to mammalian PS synthases. In this study, we characterize mutant Gong phenotypes. Adult flies with trans-heterozygous and heterozygous mutations for Gong loss-of-function alleles had reduced life span, increased bang sensitivity, locomotor defects, and increased formation of vacuoles in the brain, a sign associated with neurodegenerative disorders. Similar phenotypes were observed with pan-glial-specific knockdown/overexpression of Gong, but not with pan-neuronal manipulations. We observed defective mitochondria in the mutant adult brain, elevated production of reactive oxygen species, and increased autophagy and apoptotic cell death. These findings suggest that proper expression of Gong in glia is essential for the development and maintenance of brain function. We propose a new mechanism for neurodegenerative disease, triggered by defective PS metabolism in the nervous system.

Keywords: phosphatidylserine synthase, Longevity, Neurodegeneration, ROS, mitochondrial defect, Glia, Drosophila

Suggested Citation

Park, Ye-Jin and Kim, Sungkyung and Shim, Hyeon-Pyo and Park, Jae H. and Lee, Gyunghee and Kim, Tae-Yeop and Jo, Min-Cue and Kwon, Ah-Young and Lee, Mihwa and Kwon, Seung-Hae and Jeon, Sang-Hak, Mutations of the Gongpo Gene Encoding a Homolog of Mammalian Phosphatidylserine Synthases Cause Neurodegeneration in Drosophila Melanogaster (August 27, 2019). ISCIENCE-D-19-00877. Available at SSRN: https://ssrn.com/abstract=3443687 or http://dx.doi.org/10.2139/ssrn.3443687
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Ye-Jin Park

Seoul National University - Science Education

Korea, Republic of (South Korea)

Sungkyung Kim

Seoul National University - Science Education

Korea, Republic of (South Korea)

Hyeon-Pyo Shim

Korea Institute for Curriculum and Evaluation

Jeongdong Bldg.
21-15 Jeongdong-gil Jung-gu
Seoul,, 100-784
Korea, Republic of (South Korea)

Jae H. Park

University of Tennessee, Knoxville - Department of Biochemistry and Cellular and Molecular Biology

United States

Gyunghee Lee

University of Tennessee, Knoxville - Department of Biochemistry and Cellular and Molecular Biology

United States

Tae-Yeop Kim

Seoul National University - Science Education

Korea, Republic of (South Korea)

Min-Cue Jo

Seoul National University - Science Education

Korea, Republic of (South Korea)

Ah-Young Kwon

Seoul National University - Science Education

Korea, Republic of (South Korea)

Mihwa Lee

Seoul National University - Science Education

Korea, Republic of (South Korea)

Seung-Hae Kwon

Korea Basic Science Institute

169-148, Gwahak-ro
Yuseong-gu
Daejeon
Korea, Republic of (South Korea)

Sang-Hak Jeon (Contact Author)

Seoul National University - Science Education ( email )

Korea, Republic of (South Korea)

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