Abstract

Phosphorylation is one of the most important posttranslational modifications and regulates the physiological process. While recent studies highlight a major role of phosphorylation in the regulation of sleep–wake cycles to a lesser extent, the phosphoproteome in the suprachiasmatic nucleus (SCN) is not well-understood. Herein, we reported that the EA treatment elicits partial reparation of circadian rhythmicity when mice were exposure to constant darkness for long time. We investigated the effects of EA on circadian rhythms in constant darkness between EA stimulation and free-running control. Next, mass spectrometry–based phosphoproteome was utilized to explore the molecular characteristics of EA-induced phosphorylation modification in the SCN. A total of 6,192 distinct phosphosites on 2,488 proteins were quantified. Functional annotation analysis and protein–protein interaction networks demonstrated the most significant enriched phosphor-proteins and phosphosites involved in postsynapse and glutamatergic synapse. The current data indicated that most of the altered molecules are structural proteins. The target proteins, NMDAR and CAMK2, were selected for verification, consistent with the results of LC–MS/MS. These findings revealed a complete profile of phosphorylation modification in response to EA.

Highlights

  • The suprachiasmatic nucleus (SCN) is a mammalian master clock that regulates various circadian rhythms, such as physiology and behavior, to adapt the internal environment to changes in the external environment

  • We found that most downregulated proteins clustered in CT4 and CT8, while CT16 showed that upregulated proteins were dominant (Figure 3C). These results suggested that EA has significant effects on the phosphorylation pattern of SCN proteins

  • The current study provides a glimpse at the effects of EA-induced phase shift on the phosphoproteomic patterns in constant darkness in mice SCN

Read more

Summary

Introduction

The suprachiasmatic nucleus (SCN) is a mammalian master clock that regulates various circadian rhythms, such as physiology and behavior, to adapt the internal environment to changes in the external environment. The SCN can be entrained by zeitgeber to regulate the biological rhythms. Several studies have been conducted to examine the proteomics of the SCN to elucidate the circadian rhythm (Deery et al, 2009; Chiang et al, 2014). The posttranslational modifications (PTMs) can alter the activity of proteins involved in cell signaling. Two recent reports highlighted the role of phosphorylation in the regulation of sleep–wake cycles by allowing prompt modulation of protein activity (Wang et al, 2018; Brüning et al, 2019). Despite extensive research on phosphorylation in the liver, little is known about its role in the regulation of the SCN circadian rhythm

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call