RRC ID 33724
Author Afonso DJ, Liu D, Machado DR, Pan H, Jepson JE, Rogulja D, Koh K.
Title TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila.
Journal Curr. Biol.
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.
Volume 25(13)
Pages 1717-26
Published 2015-6-29
DOI 10.1016/j.cub.2015.05.037
PII S0960-9822(15)00611-9
PMID 26096977
PMC PMC4559600
MeSH Animals Arousal / physiology* Blotting, Western CDC2 Protein Kinase / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cyclin A / metabolism* Drosophila / physiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Gene Knockdown Techniques Neurons / physiology Pars Reticulata / cytology Pars Reticulata / physiology RNA Interference Sleep / physiology*
IF 9.251
Times Cited 9
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Drosophila 6889R-1