PMID- 29915051
OWN - NLM
STAT- MEDLINE
DCOM- 20180904
LR  - 20181114
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 115
IP  - 27
DP  - 2018 Jul 3
TI  - Serine metabolism in the brain regulates starvation-induced sleep suppression in 
      Drosophila melanogaster.
PG  - 7129-7134
LID - 10.1073/pnas.1719033115 [doi]
AB  - 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.
CI  - Copyright (c) 2018 the Author(s). Published by PNAS.
FAU - Sonn, Jun Young
AU  - Sonn JY
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, 34141 Daejeon, Republic of Korea.
FAU - Lee, Jongbin
AU  - Lee J
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, 34141 Daejeon, Republic of Korea.
FAU - Sung, Min Kyung
AU  - Sung MK
AD  - Department of Bio and Brain Engineering, Korea Advanced Institute of Science and 
      Technology, 34141 Daejeon, Republic of Korea.
FAU - Ri, Hwajung
AU  - Ri H
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, 34141 Daejeon, Republic of Korea.
FAU - Choi, Jung Kyoon
AU  - Choi JK
AD  - Department of Bio and Brain Engineering, Korea Advanced Institute of Science and 
      Technology, 34141 Daejeon, Republic of Korea.
FAU - Lim, Chunghun
AU  - Lim C
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      44919 Ulsan, Republic of Korea clim@unist.ac.kr jchoe@kaist.ac.kr.
FAU - Choe, Joonho
AU  - Choe J
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, 34141 Daejeon, Republic of Korea; clim@unist.ac.kr jchoe@kaist.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180618
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Drosophila Proteins)
RN  - 452VLY9402 (Serine)
RN  - EC 4.3.1.17 (L-Serine Dehydratase)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain/*metabolism
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Drosophila melanogaster
MH  - L-Serine Dehydratase/genetics/*metabolism
MH  - *Mutation
MH  - Serine/genetics/*metabolism
MH  - *Signal Transduction
MH  - Starvation/genetics/*metabolism
PMC - PMC6142195
OTO - NOTNLM
OT  - serine
OT  - sleep regulation
OT  - starvation
COIS- The authors declare no conflict of interest.
EDAT- 2018/06/20 06:00
MHDA- 2018/09/05 06:00
PMCR- 2018/06/18
CRDT- 2018/06/20 06:00
PHST- 2018/06/20 06:00 [pubmed]
PHST- 2018/09/05 06:00 [medline]
PHST- 2018/06/20 06:00 [entrez]
PHST- 2018/06/18 00:00 [pmc-release]
AID - 1719033115 [pii]
AID - 201719033 [pii]
AID - 10.1073/pnas.1719033115 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7129-7134. doi: 
      10.1073/pnas.1719033115. Epub 2018 Jun 18.