Molecular Sunglasses Regulate Circadian Clock

Molecular “sunglasses” ensure that the so-called internal clock of a fungus does not confuse night and day despite intrusive signals from sources like moonlight or lamplight. At night, a special protein suppresses the effect of low light intensities from, say, the moon or a lamp, thus playing a crucial role in the precise synchronisation of the internal clock with the day and night sequence outside. These findings are the outcome of a study undertaken by a research team at Heidelberg University’s Biochemistry Centre in conjunction with colleagues at the Semmelweis University, Budapest. The results of the study have now been published in the journal "Cell".

The internal clock of an organism is run by molecular pacemakers in the body cells that adapt metabolism and behaviour to the time of day. One example is the waking-sleeping rhythm. As the internal clock oscillates in periods of more or less 24 hours, it is also known as the “circadian” clock (circa dian = approximately one day). It switches a large number of genes on or off, depending on the time of day and is synchronised with external time by “zeitgeber” like light. Jet lag after travel across several time zones, for example, is indicative of a discrepancy between internal and external time. Until now, we had no knowledge of how circadian clocks stay precisely synchronised with the day-night sequence despite intrusive light signals from the environment.

With a study of the filamentous fungus Neurospora crassa, Prof. Dr. Michael Brunner’s research group at Heidelberg University’s Biochemistry Centre and the Budapest scientist Dr. Krisztina Káldi have come up with the answer to this question. The scientists used this bread mould as a model organism for the investigation of its circadian clock at the molecular level. At the heart of Neurospora’s circadian system is the transcription factor WCC, a protein that activates or “switches on” about 1,000 genes depending on the time of day. The WCC itself possesses a special switch that reacts to light, the so-called LOV domain, and thus serves as a highly sensitive light receptor synchronising the internal clock with external day.

As brightness increases with the arrival of daylight, the transcription factor WCC is “switched on” via the LOV domain and activates the genes assigned to it. Among these is a gene responsible for the production of the so-called VVD protein. VVD is also a light receptor with an LOV domain which in turn “switches off” WCC. The presence of VVD terminates the effect of WCC, thus also restricting the activation of light-dependent genes. In the night, the VVD protein produced in the course of the day functions as something like the molecular memory of the brightness of the preceding daylight. Because VVD inactivates transcription factor WCC, low light intensities, as from the moon or a lamp, are suppressed. When the light returns at the end of the night, VVD has been largely degraded so that transcription factor WCC can be switched on again. Accordingly, the VVD protein functions much like molecular sunglasses ensuring at the molecular level that the circadian clock does not mix up day and night.

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Original publication
E. Malzahn, S. Cipriandis, K. Káldi, T. Schafmeier, M. Brunner: Photo-Adaptation in Neurospora is Mediated by Competitive Interaction of Activating and Inhibitory Light-Oxygen-Voltage Domains. Cell (3 September 2010), 142(5), 762-772, doi:10.1016/j.cell.2010.08.010

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Biochemistry Centre
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michael.brunner@bzh.uni-heidelberg.de

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