Module 6: Figure circadian clock input–output signals



The proposed function of cell signalling pathways in mediating the input and output signals of the circadian clock.

The nucleus contains the circadian oscillator, which sets up fluctuations in the level of the clock components PER and BMAL1 (see Module 6: Figure circadian clock molecular mechanism for details. The activity of this circadian oscillator can be modulated by various input signals, such as the neurotransmitter glutamate, which can generate Ca2+ signals to activate Per transcription using the transcription factor cyclic AMP response element-binding protein (CREB). In addition, the circadian oscillator must communicate with the outside world. How this is done is still a mystery. Components of the clock, such as PER and BMAL1, may activate various output signals that may act by switching on various oscillatory systems, such as cytosolic Ca2+ oscillator that produces a Ca2+ oscillation with a period of 24 h (red trace). In addition, there is a much faster membrane oscillator that initiates the action potentials that make up the neuronal firing rhythm (black trace) that lags behind the Ca2+ oscillation by about 4 h.