Proteomic analysis reveals the role of synaptic vesicle cycling in sustaining the suprachiasmatic circadian clock
Open accessAbstract
The central circadian pacemaker of the suprachiasmatic nucleus (SCN) is characterized as a series of transcriptional/posttranslational feedback loops. How this molecular mechanism coordinates daily rhythms in the SCN and hence the organism is poorly understood. We conducted the first systematic exploration of the "circadian intracellular proteome" of the SCN and revealed that approximately 13% of soluble proteins are subject to circadian regulation. Many of these proteins have underlying nonrhythmic mRNAs, so they have not previously been noted as circadian. Circadian proteins of the SCN include rate-limiting factors in metabolism, protein trafficking, and, intriguingly, synaptic vesicle recycling. We investigated the role of this clock-regulated pathway by treating organotypic cultures of SCN with botulinum toxin A or dynasore to block exocytosis and endocytosis. These manipulations of synaptic vesicle recycling compromised circadian gene expression, both across the SCN as a circuit and within individual SCN neurons. These findings reveal how basic cellular processes within the SCN are subject to circadian regulation and how disruption of these processes interferes with SCN cellular pacemaking. Specifically, we highlight synaptic vesicle cycling as a novel point of clock cell regulation in mammals.
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It has been estimated that 6-20% of the murine proteome exhibits circadian rhythms in tissues such as the SCN and liver.
“Similar to the reported proportion of rhythmic transcripts, it has been estimated that 6-20% of the murine proteome exhibits circadian rhythms in tissues such as the SCN (33,34) and liver (35)(36)(37).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [33]
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- Authors
- Deery, M. J., Maywood, E. S., Chesham, J. E., Sládek, M., Karp, N. A., Green, E. W., Charles, P. D., Reddy, A. B., Kyriacou, C. P., Lilley, K. S., & Hastings, M. H.
- Affiliations
- University of Cambridge (GB)
- MRC Laboratory of Molecular Biology (GB)
- University of Leicester (GB)
- Corresponding author
- Lilley, Kathryn S.
- Hastings, Michael H.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 19
- Issue
- 23
- Pages
- 2031-2036
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2082706883
- Cited by
- 125
- References
- 41
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 6 · 2016: 5 · 2015: 9 · 2014: 10 · 2013: 15 · 2012: 9
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1324 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/C006941/1)
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- suprachiasmatic nucleus, circadian clock, synaptic vesicle recycling, exocytosis, endocytosis, botulinum toxin type A, dynasore, circadian gene expression, protein trafficking
- MeSH terms
- Animals, Biological Clocks, Brain, Gene Expression Regulation, Hydrazones, Neurotoxins, Suprachiasmatic Nucleus, Synaptic Vesicles, Botulinum Toxins, Type A, Gene Expression Profiling, Proteomics, Mice
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