title: Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila.
abstract: In the Drosophila circadian oscillator, the CLOCK/CYCLE complex activates transcription of period (per) and timeless (tim) in the evening. PER and TIM proteins then repress CLOCK (CLK) activity during the night. The pace of the oscillator depends upon post-translational regulation that affects both positive and negative components of the transcriptional loop. CLK protein is highly phosphorylated and inactive in the morning, whereas hypophosphorylated active forms are present in the evening. How this critical dephosphorylation step is mediated is unclear. We show here that two components of the STRIPAK complex, the CKA regulatory subunit of the PP2A phosphatase and its interacting protein STRIP, promote CLK dephosphorylation during the daytime. In contrast, the WDB regulatory PP2A subunit stabilizes CLK without affecting its phosphorylation state. Inhibition of the PP2A catalytic subunit and CKA downregulation affect daytime CLK similarly, suggesting that STRIPAK complexes are the main PP2A players in producing transcriptionally active hypophosphorylated CLK.
authors.affiliation: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Andreazza
authors.affiliation: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Sylvina
authors.initials: S
authors.lastname: Bouleau
authors.affiliation: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Martin
authors.affiliation: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Lamouroux
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, 91190 Gif-sur-Yvette, France.
authors.forename: Prishila
authors.initials: P
authors.lastname: Ponien
authors.affiliation: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Papin
authors.affiliation: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Chélot
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, 91190 Gif-sur-Yvette, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jacquet
authors.affiliation: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, 91190 Gif-sur-Yvette, France. Electronic address: rouyer@inaf.cnrs-gif.fr.
authors.forename: François
authors.initials: F
authors.lastname: Rouyer
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D004330:Drosophila / Q000378:metabolism*; D005260:Female; D008297:Male; D056950:Period Circadian Proteins / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D056950:Period Circadian Proteins; D056926:CLOCK Proteins