Fig. 3: The interaction between the circadian clock and mTOR-related signaling transduction pathways. | Translational Psychiatry

Fig. 3: The interaction between the circadian clock and mTOR-related signaling transduction pathways.

From: The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model

Fig. 3

Light at night activates ERK MAPK and mTORC1 pathways in the SCN by the neurotransmitter glutamate and PACAP. ERK MAPK in turn activates MSK to phosphorylate CREB and activated Per transcription. ERK MAPK also activated MNK, which in turn phosphorylates the cap-binding protein eIF4E at Ser209 and regulate mRNA translation. The mTORC1 activation also regulates translation through downstream translation pathway effectors such as S6Ks and 4E-BPs, etc. Phosphorylated S6K regulates circadian ribosomal biogenesis. Phosphorylation of 4E-BP activated eIF4E dependent translation. The ERK MAPK and mTOR pathways converge on eIF4E to regulate cap-dependent translation of Per1, Per2, Vip mRNAs, which play important roles in photic entrainment of the circadian clock and SCN cell synchronization. Circadian mTOR activities are controlled by the circadian clock via complex mechanisms, one of which may be through the interaction of Per2 with TSC1.

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