Serine metabolism in the brain regulates starvation-induced sleep suppression in Drosophila melanogaster

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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.
Publisher
NATL ACAD SCIENCES
Issue Date
2018-07
Language
English
Article Type
Article
Keywords

RNA-SEQ; ACETYLCHOLINE-RELEASE; CORTICAL SLICES; ACID; PHOSPHATIDYLSERINE; RECEPTOR; IDENTIFICATION; DEHYDRATASES; DEPRIVATION; TRANSPORTER

Citation

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.115, no.30, pp.7129 - 7134

ISSN
0027-8424
DOI
10.1073/pnas.1719033115
URI
http://hdl.handle.net/10203/244533
Appears in Collection
BiS-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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