The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period

Godinho, Sofia I. H.; Maywood, Elizabeth S.; Shaw, Linda E.; Tucci, Valter; Barnard, Alun R.; Busino, Luca; Pagano, Michele; Kendall, Rachel; Quwailid, Mohamed M.; Romero, M. Rosario; O’Neill, John S.; Chesham, Johanna E.; Brooker, Debra; Lalanne, Zuzanna; Hastings, Michael H.; Nolan, Patrick M.

doi:10.1126/science.1141138

Cited by 432 publications

(387 citation statements)

References 21 publications

Supporting

Mentioning

365

Contrasting

Unclassified

Order By: Relevance

“…Hence, PER and CRY levels are higher during the day and lower at night, similar to the SCN neural activity rhythm. The circadian time course of gene expression is regulated by post-translational mechanisms, including phosphorylation-dependent ubiquitination and proteosomal degradation of PER and CRY proteins in the cytoplasm (36)(37)(38)(39)(40) , allowing for a new cycle of transcription by relieving inhibition of the BMAL1:CLOCK/NPAS2 transcriptional complex.…”

Section: Regulation Of Clock-controlled Genes Involved In Lipid Metabmentioning

confidence: 99%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

130

View full text Add to dashboard Cite

The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

show abstract

Section: Regulation Of Clock-controlled Genes Involved In Lipid Metabmentioning

confidence: 99%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

130

View full text Add to dashboard Cite

show abstract

“…Recently, two large-scale mutagenesis projects identified two independent mutations in the same protein [49][50][51]. The FBXL3 protein is an E3-type ubiquitin ligase.…”

Section: Lessons From Micementioning

confidence: 99%

The daily rhythm of mice

2011

View full text Add to dashboard Cite

Edited by Martha Merrow and Michael BrunnerKeywords: Clock mutant mice Metabolism Cancer Neurological disease Mood Obesity a b s t r a c tThe house mouse Mus musculus represents a valuable tool for the analysis and the understanding of the mammalian circadian oscillator. Forward and reverse genetics allowed the identification of clock components and the verification of their function within the circadian clockwork. In many cases unforeseen links were discovered between a particular circadian regulatory protein and various diseases or syndromes. Thus, this model system is not only perfectly suited to pinpoint the components of the mammalian circadian clock, but also to unravel metabolic, physiological, and pathological processes linked to the circadian timing system.

show abstract

“…When analyzing the circadian accumulation patterns of dPER and mammalian PERs by western blotting, a substantial electrophoretic mobility shift of the PER bands occurred, in addition to a high-amplitude variation in protein abundance. This mobility shift has been shown ity of the CRY proteins, and a reduced expression of PER proteins Godinho et al 2007;Siepka et al 2007). Given the relatively high CRY protein amounts as well as the rather small amplitude of CRY protein abundance rhythms, the molecular basis of Fbxl3's essential role in the circadian clock is still, at least in part, obscure.…”

Section: Per Phosphorylationmentioning

confidence: 99%

Role of Phosphorylation in the Mammalian Circadian Clock

Vanselow¹,

Kramer²

2007

Cold Spring Harbor Symposia on Quantitative Biology

View full text Add to dashboard Cite

Circadian clocks regulate a wide variety of processes ranging from gene expression to behavior. At the molecular level, circadian rhythms are thought to be produced by a set of clock genes and proteins interconnected to form transcriptional-translational feedback loops. Rhythmic gene expression was formerly regarded as the major drive for rhythms in clock protein abundance, but recent findings underline the crucial importance of posttranslational mechanisms for both the generation and dynamics of circadian rhythms. In particular, the reversible phosphorylation of PER proteins-essential components within the negative feedback loop in Drosophila and mammals-seems to have a key role for the correct timing of nuclear repression. To understand how PER protein phosphorylation regulates the dynamics of the circadian oscillator, we have mapped endogenous phosphorylation sites in mPER2. Detailed investigation of the functional role of one particular phosphorylation site (Ser-659, which is mutated in the familial advanced sleep phase syndrome [FASPS]) led us propose a model of functionally different phosphorylation sites in PER2. This concept explains not only the FASPS phenotype, but also the effect of the tau mutation in hamster.

show abstract

The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period

Cited by 432 publications

References 21 publications

Circadian regulation of lipid metabolism

Circadian regulation of lipid metabolism

The daily rhythm of mice

Role of Phosphorylation in the Mammalian Circadian Clock

Contact Info

Product

Resources

About