mTOR Signaling and Entrainment of the Mammalian Circadian Clock.

The biochemistry, physiology and behavior of nearly all organisms are influenced by an inherent circadian (24 hr) clock timing mechanism. For mammals, the linchpin of this biological timing process is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. One key feature of the SCN clock is that it is tightly entrained to lighting cues, thus ensuring that the clock is synchronized to the ever-changing seasonal light cycle. Within the field of circadian biology, there has been intense interest in understanding the intracellular signaling events that drive this process. To this end, our recent studies have revealed a role for an evolutionarily conserved translational control kinase, the mammalian target of rapamycin (mTOR), in the SCN clock entrainment process. Here we provide an overview of mechanisms of inducible mTOR activation in the SCN, and describe the effects of mTOR on clock protein synthesis and behavioral rhythmicity. Given that dysregulation of SCN timing has been associated with an array of clinical conditions (e.g., hypertension, obesity, diabetes, depression), new insights into the molecular mechanisms that regulate clock timing may provide new therapeutic treatments for circadian rhythm-associated disorders.