Drosophila ATF-2 Regulates Sleep and Locomotor Activity in Pacemaker Neurons

Abstract

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_vs) and also, to a much lesser extent, in small ventral lateral neurons, the pacemaker neurons. Only l-LN_vs were stained with the antibody that specifically recognizes phosphorylated dATF-2, suggesting that dATF-2 is activated specifically in l-LN_vs. 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.

ACKNOWLEDGMENTS

We are grateful to R. Ueda for the UAS-dATF-2IR R-2 flies, F. Rouyer for the anti-PDF antibody, A. Sehgal for the anti-TIM antibody, T. Nagao for valuable discussions, the NIG-Fly stock center for the RNAi line of dATF-2, and the Bloomington Stock Center for fly strains.

This work was supported in part by grants-in-aid for scientific research and by grants from the Genome Network Project of the Ministry of Education, Culture, Sports, Science, and Technology of Japan.