title: TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila.
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.
authors.affiliation: Department of Neuroscience, Farber Institute for Neurosciences and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's, PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal.
authors.forename: Dinis J S
authors.initials: DJ
authors.lastname: Afonso
authors.affiliation: Department of Neuroscience, Farber Institute for Neurosciences and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Die
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, Farber Institute for Neurosciences and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's, PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Machado
authors.affiliation: Department of Neuroscience, Farber Institute for Neurosciences and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Huihui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Neuroscience, Farber Institute for Neurosciences and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: James E C
authors.initials: JE
authors.lastname: Jepson
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Dragana
authors.initials: D
authors.lastname: Rogulja
authors.affiliation: Department of Neuroscience, Farber Institute for Neurosciences and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: kyunghee.koh@jefferson.edu.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Koh
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology*; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D009474:Neurons / Q000502:physiology; D065841:Pars Reticulata / Q000166:cytology / Q000502:physiology; D034622:RNA Interference; D012890:Sleep / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D029721:Drosophila Proteins; C454818:tara protein, Drosophila; D016203:CDC2 Protein Kinase; C000601753:Cdk1 protein, Drosophila