LIGHT INPUT PATHWAYS

Cyanobacteria 

In cyanobacteria, a gene called circadian input kinase A (cikA) is involved in the light input pathway. CikA is a bacteriophytochrome that also contains a histidine kinase. In plants phytochromes transmit light to the plant biological clock (Somers et al. 1998). It is not clear whether CikA plays the same role in cyanobacteria, as although it contains a sequence close to that of other phytochromes and bacteriophytochromes, cikA does not contain a conserved cys ligand that is involved in the binding of chromophores in other phytochromes. It may be that cikA does not act as a photoreceptor. However it is known that inactivation of cikA in cyanobacteria causes a phase delay of 2 hours, changes the phase of genes that peak at dawn, and nearly abolishes phase resetting by dark pulses (Schmitz et al. 2000). 

In cyanobacteria, it is likely that the input mechanism, whether it be CikA or an unknown one, acts on KaiC as this is the protein that if expresses when it is normally at low levels, resets the clock (Xu et al 2000).

Neurospora

In Neurospora, the clock is reset by the actions of light on the proteins WC-1 and WC-2. This causes the rapid transcriptional induction of frq. It is possible that WC-1 is both a transcription factor and a photoreceptor, as it contains a domain similar to one found in a plant blue light photoreceptor (Harmer et al. 2000). Light also plays a part in the degradation of WC-1 which becomes progressively phosphorylated in response to light. This eventually leads to its degradation. (Green 1998). It is thought that FRQ also has a role to play in light entrainment, possibly acting as a gateway through which light signals must pass (Merrow et al. 2001).

Drosophila

The key molecular event in the Drosophila light response is the degradation of dTIM. dTIM is rapidly degraded by light. As dTIM stabilises dPER, the indirect effect of light is to increase the levels of degradation of dPER. The result of these degradations result in phase shifts. In early evening, when dPER and dTIM levels are accumulating, a light pulse causing degradation of the protein would reduce the levels, causing a phase delay. On the other hands, a light pulse in the late night when dPER/ dTIM levels are decreasing would cause further decreases in the levels of these proteins, causing an advance in the cycle.

The degradation of dTIM is mediated by the protein CRYPTOCHROME (dCRY) which acts on the dPER/ dTIM heterodimers in the presence of light, preventing it from acting on the dper/ dtim genes and blocking their transcription (Ceriani et al. 1999). As in this circumstance dTIM degradation by light does not occur, the net result is an increase in the levels of the dPER/ dTIM heterodimers in light.

Mammals

In mammals, the principal photoreceptor is the retina. Signals pass from here to the SCN via the retinohypothalamic tract (RHT). The SCN then translates the signal into a change in rhythm. Unlike Drosophila, there are many intermediate steps between the photoreceptors and the oscillators, allowing the integration of signal from other sources.

Although it is known that the retina is the principal light-detecting organ in mammals, the exact molecule that passes the signal from the eye to the oscillator. Mice lacking all rod and most cone cells (and hence the molecules rhodopsin and opsin) can still be entrained by light, indicating that these are not involved, whilst the cryptochromes mCRY1 and mCRY2, although playing an important role in the mammalian clock also do not appear to be the photoreceptors in the circadian clock, as mice lacking both cryptochromes still show oscillating expression of mPER2 under LD conditions in the SCN (Selby et al 2000).

In the mammalian circadian rhythm, the clock protein responsible for clock resetting by light appears to be mPER1. Transcription of mper1 is rapidly induced after short bursts of light (Shigeyoshi et al 1997). However there is still a delay between transcription of the gene and the appearance of the mPER1 protein (Field et al. 2000). Increasing levels of mPER1 using light has an effect on phase shifting. Induction of mPER1 in the early evening when levels of the protein are falling causes a delay in the decline, resulting a phase delay. If the induction occurs in the late night when levels of mPER1 are rising, there is a rapid increase of mPER levels resulting in a phase advance.

Light also has effects on other molecule in the SCN. This includes the phosphorylation of cyclic AMP (cAMP) Response Element-Binding protein (CREB). Phosphorylated CREB activates transcription in genes containing cAMP Response Elements (CREs) in their promoter. mper1 contains 4 CREs in its promoter region (Hida et al 2000). It has not yet been shown whether mPER1 is directly activated by phospho-CREB. However if this is shown, CREB may provide a means for multiple signals to act on the oscillator to reset is as it can be phosphorylated by many different kinases (Harmer et al. 2001)

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