Analysis of Clock Proteins in Mouse SCN Demonstrates Phylogenetic Divergence of the Circadian Clockwork and Resetting Mechanisms

Abstract

The circadian clock in the suprachiasmatic nuclei (SCN) is comprised of a cell-autonomous, autoregulatory transcriptional/translational feedback loop. Its molecular components include three period and two cryptochrome genes. We describe circadian patterns of expression of mPER2 and mPER3 in the mouse SCN that are synchronous to those for mPER1, mCRY1, and mCRY2. Coimmunoprecipitation experiments demonstrate in vivo associations of the SCN mPER proteins with each other and with the mCRY proteins, and of mCRY proteins with mTIM, but no mPER/mTIM interactions. Examination of the effects of weak and strong resetting light pulses on SCN clock proteins highlights a central role for mPER1 in photic entrainment, with no acute light effects on either the mCRY or mTIM proteins. These clock protein interactions and photic responses in mice are divergent from those described in Drosophila.

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

“…The anatomical boundaries of the SCN, defined by cell density, correspond well with functional markers such as 2-deoxyglucose utilization [26], c-fos expression [17], and the expression of genes involved in the generation of circadian oscillations ("clock genes") [9]. Accordingly, although other tissues and cells are known to express endogenous molecular oscillations, SCN neurons are functionally distinct from surrounding hypothalamic neurons.…”

Forebrain oscillators ticking with different clock hands

“…PER2 expression has also been reported in limbic structures, such as amygdala and bed nucleus of the stria terminalis (Amir et al, 2004;Lamont et al, 2005). Except for the SCN in which the rhythm of PERs follows the mRNA expression by 4-6 h (Field et al, 2000;Mendoza et al, 2007), little is known about the exact timing of both PER1 and PER2 oscillations in forebrain structures. For that purpose, we investigated the daily patterns of PER1 and PER2 expression throughout the forebrain in mice fed ad libitum.…”

The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase–response curve amplitude

“…In principle, entrainment of the core circadian clock mechanism described above would be expected to occur as a consequence of either phasic or tonic changes in the levels of oscillating feedback elements (e.g., the PER or CRY proteins). Within the core circadian clock mechanism, the only elements that have been definitively found to be light responsive in the suprachiasmatic nucleus (SCN) are the Per1 and Per2 genes (8)(9)(10)(11)(12)(13)(14). Acute light exposure of mice causes phasedependent elevations of Per1 and Per2 mRNA and protein levels in the SCN.…”