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Proc. Natl. Acad. Sci. USA, Published ahead of print June 18, 2018 | https://doi.org/10.1073/pnas.1719033115
Serine metabolism in the brain regulates starvation-induced sleep suppression in Drosophila melanogaster
Jun Young Sonna,1, Jongbin Leea,1, Min Kyung Sungb, Hwajung Ria, Jung Kyoon Choib, Chunghun Limc,2, and Joonho Choea,2
aDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, 34141 Daejeon, Republic of Korea; bDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 34141 Daejeon, Republic of Korea; and cSchool of Life Sciences, Ulsan National Institute of Science and Technology, 44919 Ulsan, Republic of Korea
1J.Y.S. and J.L. contributed equally to this work.
aDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, 34141 Daejeon, Republic of Korea; bDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 34141 Daejeon, Republic of Korea; and cSchool of Life Sciences, Ulsan National Institute of Science and Technology, 44919 Ulsan, Republic of Korea
1J.Y.S. and J.L. contributed equally to this work.
2To whom correspondence may be addressed.
Abstract
Sleep and metabolism are physiologically and behaviorally intertwined; however, the molecular basis for their interaction remains poorly understood. Here, we identified a serine metabolic pathway as a key mediator for starvation-induced sleep suppression. Transcriptome analyses revealed that enzymes involved in serine biosynthesis were induced upon starvation in Drosophila melanogaster brains. Genetic mutants of astray (aay), a fly homolog of the rate-limiting phosphoserine phosphatase in serine biosynthesis, displayed reduced starvation-induced sleep suppression. In contrast, a hypomorphic mutation in a serine/threonine-metabolizing enzyme, serine/threonine dehydratase (stdh), exaggerated starvation-induced sleep suppression. Analyses of double mutants indicated that aay and stdh act on the same genetic pathway to titrate serine levels in the head as well as to adjust starvation-induced sleep behaviors. RNA interference-mediated depletion of aay expression in neurons, using cholinergic Gal4 drivers, phenocopied aay mutants, while a nicotinic acetylcholine receptor antagonist selectively rescued the exaggerated starvation-induced sleep suppression in stdh mutants. Taken together, these data demonstrate that neural serine metabolism controls sleep during starvation, possibly via cholinergic signaling. We propose that animals have evolved a sleep-regulatory mechanism that reprograms amino acid metabolism for adaptive sleep behaviors in response to metabolic needs.
starvation | sleep regulation | serine
starvation | sleep regulation | serine
논문정보
- Research article
- 2018년 06월 (BRIC 등록일 2018-06-25)
- 국내 연구진
- 생명과학 > 생화학
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