Fig. 4: Molecular model of light-induced signalling pathways for clock phase shifting.
From: Beyond vision: effects of light on the circadian clock and mood-related behaviours
The left part of the model depicts the phase delay process involving T-type voltage-gated calcium channels (VGCCs), and the right part illustrates a hypothetical phase advance process involving L-type VGCCs. The delay model involves activating glutamate signalling via protein kinase A (PKA), Cav 3.1, Ca2+/calmodulin-dependent protein kinase (CaMK), and cAMP response element-binding protein (CREB), which binds to CRE promoter elements of target genes such as Per1, Dec1, Sik1, and Gem. This transcriptional activation is supported by co-factors such as CREB-regulated transcription coactivator 1 (CRTC1), CREB-binding protein (CBP), and PER2. PER2 and PKA are regulated by Cdk5, whose activity depends on interaction with p35/25, which is influenced by light and opioids. The phase advance mechanism is unclear (hatched arrows) and may involve the MEK/ERK signalling pathway, which may also influence phase delays and FOS/JUN transcriptional activation.
