1. TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila
- Author
-
James E.C. Jepson, Kyunghee Koh, Die Liu, Huihui Pan, Dragana Rogulja, Daniel R Machado, Dinis J.S. Afonso, and Universidade do Minho
- Subjects
Medicina Básica [Ciências Médicas] ,Cyclin A ,Blotting, Western ,Cell Cycle Proteins ,General Biochemistry, Genetics and Molecular Biology ,Article ,RNA interference ,CDC2 Protein Kinase ,Pars Reticulata ,Animals ,Drosophila Proteins ,Genetics ,Neurons ,Cyclin-dependent kinase 1 ,Gene knockdown ,Science & Technology ,biology ,Agricultural and Biological Sciences(all) ,Kinase ,Biochemistry, Genetics and Molecular Biology(all) ,3. Good health ,Gene Knockdown Techniques ,Mushroom bodies ,Ciências Médicas::Medicina Básica ,biology.protein ,Drosophila ,RNA Interference ,General Agricultural and Biological Sciences ,Arousal ,Sleep ,Drosophila Protein - Abstract
Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically and physically interacts with CycA to promote sleep. Furthermore, decreased levels of Cyclin-dependent kinase 1 (Cdk1), a kinase partner of CycA, rescue the short-sleeping phenotype of tara and CycA mutants, while increased Cdk1 activity mimics the tara and CycA phenotypes, suggesting that Cdk1 mediates the role of TARA and CycA in sleep regulation. Finally, we describe a novel wake-promoting role for a cluster of ∼14 CycA-expressing neurons in the pars lateralis (PL), previously proposed to be analogous to the mammalian hypothalamus. We propose that TARANIS controls sleep amount by regulating CycA protein levels and inhibiting Cdk1 activity in a novel arousal center., National Institutes of Health (R01GM088221 to K.K.) and predoctoral fellowships from the Portuguese Foundation for Science and Technology (SFRH/BD/51726/2011 to D.J.S.A. and SFRH/BD/52321/2013 to D.R.M.). Sequencing was performed at the Kimmel Cancer Center Nucleic Acid Facility, which is supported by a grant from the NIH (P30CA56036)
- Published
- 2015