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Clockwork in the eye of a fly

The blue-light pigment cryptochrome is important in regulating the circadian clock of many organisms. Scientists have now discovered that in the fruit fly Drosophila it also intervenes in the visual process. The central experiments involved were conducted at the University of Würzburg's Biocenter.

Timing is everything in the life of all organisms: plants sprout when spring is coming, bees know what flowers are open at what time of year, people tire in the evening and wake up again in the morning, and even single-celled organisms possess a circadian clock. The fruit fly Drosophila melanogaster also has a series of so-called clock genes that dictate its behavior.

With regard to the timing mechanism of the fruit fly, scientists from the universities of Padua, Ferrara, and Würzburg have now discovered a surprising detail: "We have been able to show that the blue-light pigment cryptochrome in the eye of the fly interacts with an important component of the phototransduction cascade, the protein complex InaD," says Professor Charlotte Förster. The researchers present their work in the current issue of the scientific journal PNAS.

Charlotte Förster has been a professor at the University of Würzburg since September 2009 and chairs its Department of Neurobiology and Genetics. Chronobiology, the temporal order of all living organisms, is this biologist's specialty. She is also a spokesperson for the Collaborative Research Center "Insect timing: mechanisms, plasticity and interactions", which began its work at the start of this year. It too addresses the question of how circadian clocks work in the animal kingdom.

Intervention in the visual process

The fact that cryptochrome intervenes in the visual process, is news to the science world. "Until now, cryptochrome was regarded as an important photoreceptor in the circadian clock of the fly," says Förster. In special nerve cells known as clock neurons, cryptochrome interacts with the clock protein Timeless upon exposure to light and ensures that this protein is degraded. It was not previously known that cryptochrome had any effect on the visual process and therefore on the membranes of photoreceptor cells.

These molecular processes were uncovered by scientists from Italy involved in the publication. Charlotte Förster's team was responsible for the corresponding behavioral experiments that made it possible to prove on a living object that cryptochrome does indeed influence the visual process.

The experiments

"The light sensitivity of the eyes is modulated in all animals by the circadian clock," explains Charlotte Förster. Eyes are generally more sensitive at night than during the day. In flies, the easiest way to test light sensitivity is with behavioral experiments. For this purpose, the scientists measured the tendency of the insects to approach a light source or to follow a stripe pattern rotating around them. "Both responses are stronger at night, when the photoreceptor cells of the eye are more sensitive, than during the day," says the biologist. In fact, Förster's colleague, Matthias Schlichting, revealed in his experiments that flies lacking the gene for cryptochrome do not exhibit this rhythm. Their response permanently remains at the minimum level that is measurable during daytime.

Measurement on the retina

Since these measurable behavioral responses are "at the end of the whole visual process", so to speak, and can be altered by numerous external and internal influences, the scientists also measured the light sensitivity of the eye using direct means. This was the responsibility of Rudi Grebler, another member of Förster's department. Grebler measured, among other things, the response of the cells in the retina of flies when presented with a flash of light. This revealed that in this case, too, the light sensitivity of the eye of flies lacking the gene for cryptochrome was altered in the same way as in the behavioral experiments: there was no circadian modulation, and the photoreceptor cells of the eye no longer demonstrated maximal sensitivity.

The scientists therefore drew the following conclusion: "Cryptochrome seems to be an important mediator between the circadian clock and the light sensitivity of the eye. This appears to happen through interaction with the protein InaD."

"Fly cryptochrome and the visual system". Gabriella Mazzotta, Alessandro Rossi, Emanuela Leonardi, Moyra Mason, Cristiano Bertolucci, Laura Caccin, Barbara Spolaore, Alberto J. M. Martin, Matthias Schlichting, Rudi Grebler, Charlotte Helfrich-Förster, Stefano Mammi, Rodolfo Costa and Silvio C. E. Tosatto. PNAS Online Early Edition, March 25, 2013. www.pnas.org/cgi/doi/10.1073/pnas.1212317110

Contact Prof. Dr. Charlotte Förster, +49 (0)931 31-88823, charlotte.foerster@biozentrum.uni-wuerzburg.de

idw :: 03.04.2013