Circadian Rhythm

Jeffrey C. Hall, Michael Rosbash and Michael W. Young won the 2017 Nobel Prize in Physiology or Medicine for their work identifying the mechanistic basis for the circadian rhythm in fruit flies. Circadian rhythms are physical, behavioral, and mental changes that respond primarily to the light and darkness cycle in an organism's environment. They are found in most living things, including animals, plants, and many microbes. The study of these cyclic, physiological rhythms is generally termed chronobiology (1).

The protein factors constituting the components of this circadian clock are found in almost all of the body’s organ systems (1). The primary mammalian circadian clock is located in the suprachiasmatic nuclei in the hypothalamus. The molecular mechanism for the oscillation of the circadian rhythm involves a transcription-translation feedback loop of clock genes expressed by almost all cells. In particular, BMAL1, CLOCK, PERs, and CRYs play central roles in the oscillation of the circadian rhythm and rhythmically regulate downstream gene expression (Fig. 1). Disruption of the circadian rhythm and polymorphisms in circadian rhythm-related genes are associated with various disorders, such as neurodegeneration, infertility, and sleep disturbance (Table 1) (1).

 

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Fig. 1. BMAL1 and CLOCK form a heterodimer that binds to the regulatory region (E-box) of Per1/2 and Cry1/2 to positively regulate transcription. PER and CRY proteins then form a complex and negatively regulate the transcriptional effects of BMAL1 and CLOCK.

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PER2 antibody GTX129688	BMAL1 antibody [N1N3] GTX105060	CRY1 antibody GTX132177	CLOCK antibody GTX134464

Timeless antibody GTX129604	ROR alpha antibody [C3], C-term GTX108201

Table 1.

Disrupted gene Physiological effects Bmal1 Infertility, Progressive arthropathy, Abnormal gluconeogenesis, Abnormal lipogenesis, Altered sleep pattern. Clocka Metabolic syndrome, Abnormal gluconeogenesis, Abnormal behavioral sensitization to psychostimulants, Altered sleep pattern. Per1 Abnormal apoptosis/cancer development, Abnormal behavioral sensitization to psychostimulants. Per2 Improper cell division/cancer development, Abnormal behavioral sensitization to psychostimulants, Improper alcohol intake, FASPS. Per3 Associated with DSPS. Cry1;Cry2 Altered sleep pattern. Rorα Cerebellar ataxia, Abnormal bone metabolism. Rorβ Locomotor difficulties, Retinal degeneration/blindness, Male reproductive abnormality. Rorγ Lack of lymphoid organ development, Abnormal lymphocyte homeostasis. NPAS2 Altered sleep pattern, Impaired memory. CK1ε/CK1δ FASPS

^aClock^Δ19/Δ19 mutation.

 

References:

Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R271-7.