Figure 1. Feedback loops within the Neurospora circadian system. Dual functions of FRQ proteins allow them to participate in multiple feedback loops in the Neurospora clock. In the dark the WC 1 and WC 2 proteins form a White Collar Complex (WCC) that activates gene expression from frq and clock-controlled gene (ccg) promoters. Light induction of frq and the ccgs is also mediated by the WCC (light grey arrows). frq mRNA is translated to make FRQ proteins that have two roles: first they feed back into the nucleus to block rapidly the positive effect of the WCC in driving frq transcription; second, FRQ acts, possibly in the cytoplasm, to promote the synthesis of new WC 1. Phosphorylation of FRQ triggers its turnover and is a major determinant of period length in the clock; the role of WC 1 phosphorylation is unknown. The ccgs encode proteins involved in stress responses, intermediary metabolism, and regulation of development, and collectively coordinate the developmental potential of the organism so that asexual spores are made in the early morning. Adapted from Dunlap (1999).

Figure 2. How the Neurospora clock is reset by light and temperature changes. (a) How the clock is reset by light. Shown in grey is the daily circadian cycle in abundance of the frq mRNA in the dark (y-axis on the left). Superimposed on this, in black boxes, is the response of the clock to short-duration light treatments. With respect to the y-axis on the right and the ‘0 line’ that represents no resetting response to light, light perceived in the late night or early morning advances the rhythm into the day (plotted as positive numbers up to 12 h), whereas light seen in the late day or early in the evening delays the phase of the oscillation back into the previous day (plotted as negative numbers from 0 to –6 h). Light acts rapidly through the WC proteins to induce transcriptionally the frq gene. If frq mRNA levels are already slowly rising (as they are late in the night), this rapid induction brings frq mRNA levels prematurely to their peak and results in an advance of the clock into the day phase. If frq mRNA levels are slowly falling (as they are late in the day), this rapid increase returns frq mRNA levels to their peak and results in a delay back to the day phase. Adapted from Dunlap (1999). (b) How temperature resets the Neurospora clock. Black lines follow the cycle of FRQ protein levels through the day at low temperature (lower curve) and at higher temperatures (upper curve) within the physiological range; grey arrows track the effect of temperature steps up and steps down. For steps up, all the points on the lower-temperature curve are low compared with the high-temperature curve, so the clock is reset to the time corresponding to the low point in FRQ – near to subjective dawn. For steps down the reverse is true – all the points on the higher-temperature curve are high compared with the low-temperature curve, so the clock is reset to the time corresponding to the high point in FRQ – late day to subjective dusk. Adapted from Dunlap (1999).