SUR-8 interacts with PP1-87B to stabilize PERIOD and regulate circadian rhythms in Drosophila


Autoři: Yongbo Xue aff001;  Joanna C. Chiu aff002;  Yong Zhang aff001
Působiště autorů: Department of Biology, University of Nevada, Reno, NV, United States of America aff001;  Department of Entomology and Nematology, University of California, Davis, CA, United States of America aff002
Vyšlo v časopise: SUR-8 interacts with PP1-87B to stabilize PERIOD and regulate circadian rhythms in Drosophila. PLoS Genet 15(11): e1008475. doi:10.1371/journal.pgen.1008475
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008475

Souhrn

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.

Klíčová slova:

Circadian oscillators – Circadian rhythms – Cytoplasm – Chronobiology – Neurons – Phosphatases – Phosphorylation – RNA interference


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