Molecular Mechanism of Photic Entrainment of Mammalian Circadian Clock

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Generation and entrainment of circadian clock is innevitable for mammals to cope with environmental changes and maintain the homeostasis of internal body conditions. In mammals, the circadian clock is located at the suprachiasmatic nucleus of the hypothalamus (SCN), which is synchronized to the environmental 24h rhythms mainly by light stimulation. A series of studies in this laboratory have suggested that, in addition, the SCN has inevitable roles in regulation of the autonomic nervous systems. The SCN has direct neuronal inputs from the retina that leads to synchronization of the circadian clock to the environmental light/dark cycles. In this research projects, we have examined the changes in protein phosphorylation in the SCN during the light/dark cycles and found that BIT/SHPS-1 underwent tyrosine phosphorylation in response to the lightness of the environment. BIT/SHPS-1 is a transmembrane glycoprotein on the neuronal cell surfaces implicated in signal transduction of various extracellular stimuli.Anti-BIT monoclonal antibody that stimulates its tyrosine phosphorylation induced circadian phase shifts of locomotor activity and enhanced sympathetic nerve activities. It was also tyrosine-phosphorylated on cold-exposure or 2-deoxyglucose injection. These results indicate that BIT/SHPS-1 is involved in the photic entrainment and the regulation of the autonomic nervous system by the SCN.