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A role for O-GlcNAcylation in setting circadian clock speed
Eun Young Kim1, Eun Hee Jeong, Sujin Park
1Neuroscience Graduate Program, Institute for Medical Sciences, Ajou University School of Medicine, Wonchon-dong, Suwon, Kyunggi-do, Korea. ekim@ajou.ac.kr
Genes & Development
|February 14, 2012
Summary
O-linked N-acetylglucosamine (O-GlcNAc) modification regulates the speed of circadian rhythms by altering the timing of PERIOD protein nuclear entry. This post-translational modification also stabilizes PERIOD proteins, impacting clock function.
Area of Science:
- Chronobiology
- Molecular Biology
- Biochemistry
Background:
- Circadian clocks regulate daily biological rhythms, with protein phosphorylation being crucial for their timing.
- PERIOD (PER) proteins are key regulators of circadian clock speed, exhibiting daily changes in abundance and localization.
- The precise mechanisms controlling PER protein dynamics and circadian timing are still under investigation.
Purpose of the Study:
- To investigate the role of O-linked N-acetylglucosamine (O-GlcNAc) modification in circadian clock regulation.
- To determine if O-GlcNAc transferase (OGT) influences circadian behavioral rhythms and PERIOD protein function.
- To elucidate the specific contribution of O-GlcNAc to the timing and stability of PERIOD proteins.
Main Methods:
- Utilized Drosophila melanogaster as a model organism.
- Manipulated the expression of O-GlcNAc transferase (ogt) in clock cells via knockdown and overexpression.
- Assessed circadian behavioral rhythms and analyzed the O-GlcNAcylation status and subcellular localization of the Drosophila PERIOD (dPER) protein.
Main Results:
- Altering Drosophila O-GlcNAc transferase (ogt) levels in clock cells modified circadian rhythm length.
- The Drosophila PERIOD protein (dPER) was identified as a direct target of OGT, with O-GlcNAcylation occurring predominantly at night.
- O-GlcNAcylation of dPER was found to delay its nuclear entry and OGT stabilized dPER, impacting circadian timing.
Conclusions:
- O-GlcNAcylation is a critical post-translational modification that contributes to setting the pace of circadian clocks.
- O-GlcNAcylation of dPER delays its nuclear translocation, thereby regulating circadian rhythm timing.
- OGT-mediated O-GlcNAcylation plays multiple roles in the circadian timing system, including protein stabilization and nuclear entry regulation.
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