Abstract
The timing of behavior under natural light-dark conditions is a function of circadian clocks and photic input pathways, but a mechanistic understanding of how these pathways collaborate in animals is lacking. Here we demonstrate in Drosophila that the Phosphatase of Regenerating Liver-1 (PRL-1) sets period length and behavioral phase gated by photic signals. PRL-1 knockdown in PDF clock neurons dramatically lengthens circadian period. PRL-1 mutants exhibit allele-specific interactions with the light- and clock-regulated gene timeless (tim). Moreover, we show that PRL-1 promotes TIM accumulation and dephosphorylation. Interestingly, the PRL-1 mutant period lengthening is suppressed in constant light, and PRL-1 mutants display a delayed phase under short, but not long, photoperiod conditions. Thus, our studies reveal that PRL-1-dependent dephosphorylation of TIM is a core mechanism of the clock that sets period length and phase in darkness, enabling the behavioral adjustment to change day-night cycles.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 138-149.e5 |
| Journal | Current Biology |
| Volume | 31 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 11 2021 |
Funding
We would like to thank Bloomington Drosophila Stock Center; VDRC; DGRC; Drs. Amita Sehgal, Michael Young, and Leslie Saucedo for fly stocks; and Marco Gallio and Michael Alpert for comments on the manuscript. BestGene, generated transgenic flies. Cell sorting was performed by Flow Cytometry Core Facility at Northwestern University. Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center and P41 GM108569 awarded to the National Resource for Trasnlational and Developmental Proteomics. This work was supported by National Institutes of Health (NIH) grant R01NS106955 and DARPA grant D12AP00023. The content of the information does not necessarily reflect the position or the policy of the United States government, and no official endorsement should be inferred. Conceptualization, R.A. M.R. and E.K.-E.; Methodology, R.A. E.K.-E. E.Y. and B.C.L.; Investigation, E.K.-E. D.H.L. I.S. E.Y. D.C.L. H.-K.H. and B.C.L.; Writing – Original Draft, E.K.-E. E.Y. D.C.L. H.-K.H. and R.A.; Writing – Review & Editing, E.K.-E. B.C.L. E.Y. D.C.L. H.-K.H. M.R. and R.A.; Funding Acquisition, R.A. and M.R.; Supervision, J.B. M.R. and R.A. The authors declare no competing interests. We would like to thank Bloomington Drosophila Stock Center; VDRC; DGRC; Drs. Amita Sehgal, Michael Young, and Leslie Saucedo for fly stocks; and Marco Gallio and Michael Alpert for comments on the manuscript. BestGene, generated transgenic flies. Cell sorting was performed by Flow Cytometry Core Facility at Northwestern University. Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center and P41 GM108569 awarded to the National Resource for Trasnlational and Developmental Proteomics . This work was supported by National Institutes of Health (NIH) grant R01NS106955 and DARPA grant D12AP00023 . The content of the information does not necessarily reflect the position or the policy of the United States government, and no official endorsement should be inferred.
Keywords
- Drosophila
- circadian
- phosphorylation
- photoperiod
- seasonality
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Agricultural and Biological Sciences