Drosophila ATF-2 regulates sleep and locomotor activity in pacemaker neurons.
Stress-activated protein kinases such as p38 regulate the activity of transcription factor ATF-2. However, the physiological role of ATF-2, especially in the brain, is unknown. Here, we found that Drosophila melanogaster ATF-2 (dATF-2) is expressed in large ventral lateral neurons (l-LN(v)s) and also, to a much lesser extent, in small ventral lateral neurons, the pacemaker neurons. Only l-LN(v)s were stained with the antibody that specifically recognizes phosphorylated dATF-2, suggesting that dATF-2 is activated specifically in l-LN(v)s. The knockdown of dATF-2 in pacemaker neurons using RNA interference decreased sleep time, whereas the ectopic expression of dATF-2 increased sleep time. dATF-2 knockdown decreased the length of sleep bouts but not the number of bouts. The ATF-2 level also affected the sleep rebound after sleep deprivation and the arousal threshold. dATF-2 negatively regulated locomotor activity, although it did not affect the circadian locomotor rhythm. The degree of dATF-2 phosphorylation was greater in the morning than at night and was enhanced by forced locomotion via the dp38 pathway. Thus, dATF-2 is activated by the locomotor while it increases sleep, suggesting a role for dATF-2 as a regulator to connect sleep with locomotion.
Shimizu
Hideyuki
H
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Ibaraki 305-0074, Japan.
Shimoda
Masami
M
Yamaguchi
Terumi
T
Seong
Ki-Hyeon
KH
Okamura
Tomoo
T
Ishii
Shunsuke
S
D051698:Activating Transcription Factor 2; D000818:Animals; D001143:Arousal; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002940:Circadian Rhythm; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D012890:Sleep / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
C519913:ATF-2 protein, Drosophila; D051698:Activating Transcription Factor 2; D050976:Basic-Leucine Zipper Transcription Factors; D029721:Drosophila Proteins; C096445:tim protein, Drosophila