Ryanodine receptors are regulated by the circadian clock and implicated in gating photic entrainment.

摘要

In mammals, 24h rhythms are orchestrated by the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian clock function has three components: the mechanism (the "gears"), output (the "hands"), and input (the "set" switch). Rhythmicity is maintained by molecular "gears" in which the CLOCK/BMAL1 heterodimer binds to the promoter regions of Period (Perl and Perl) and Cryptochrome (Cryl and Cry2) genes, activating transcription (Fig. 1A). Negative control of transcription occurs when PER/ CRY dimerize, are phosphorylated by casein kinase I, and translocate into the nucleus, where they inhibit their own transcription. The interaction of these feedback loops results in rhythmic expression of Per and Cry with a peak during the day and a nadir during the night (Fig. 1B) [for review, see Takahashi et al. (2008)]. The output, or "hands" of the clock, is reflected by changes in membrane physiology and in gene expression mediated by the molecular clock gears.