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- Title
SUR-8 interacts with PP1-87B to stabilize PERIOD and regulate circadian rhythms in Drosophila.
- Authors
Xue, Yongbo; Chiu, Joanna C.; Zhang, Yong
- Abstract
Circadian rhythms are generated by endogenous pacemakers that rely on transcriptional-translational feedback mechanisms conserved among species. In Drosophila, the stability of a key pacemaker protein PERIOD (PER) is tightly controlled by changes in phosphorylation status. A number of molecular players have been implicated in PER destabilization by promoting PER progressive phosphorylation. On the other hand, there have been few reports describing mechanisms that stabilize PER by delaying PER hyperphosphorylation. Here we report that the protein Suppressor of Ras (SUR-8) regulates circadian locomotor rhythms by stabilizing PER. Depletion of SUR-8 from circadian neurons lengthened the circadian period by about 2 hours and decreased PER abundance, whereas its overexpression led to arrhythmia and an increase in PER. Specifically SUR-8 promotes the stability of PER through phosphorylation regulation. Interestingly, downregulation of the protein phosphatase 1 catalytic subunit PP1-87B recapitulated the phenotypes of SUR-8 depletion. We found that SUR-8 facilitates interactions between PP1-87B and PER. Depletion of SUR-8 decreased the interaction of PER and PP1-87B, which supports the role of SUR-8 as a scaffold protein. Interestingly, the interaction between SUR-8 and PER is temporally regulated: SUR-8 has more binding to PER at night than morning. Thus, our results indicate that SUR-8 interacts with PP1-87B to control PER stability to regulate circadian rhythms. Author summary: Circadian clocks govern daily rhythms in physiology and behavior. Conserved molecular machinery drives circadian clocks among animals. PERIOD is a key pacemaker protein in fruit flies that undergoes a series of post-translational modifications. Several kinases have been identified in destabilizing PER. Here we identify the role of SUR-8 in circadian locomotor rhythms. Depletion of SUR-8 in pacemaker neurons slows down circadian rhythms and reduces PER abundance. Indeed, SUR-8 promotes the stability of PER. Finally we characterize SUR-8 as a scaffold protein to bridge PER and a phosphatase (PP1-87B) together to regulate PER phosphorylation and abundance.
- Subjects
SCAFFOLD proteins; DROSOPHILA; RAS proteins; PHOSPHOPROTEIN phosphatases; FRUIT flies; CIRCADIAN rhythms; CARDIAC pacemakers; POST-translational modification
- Publication
PLoS Genetics, 2019, Vol 15, Issue 11, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1008475