New Gear in Mouse Clock?

New proteins found in the eye may explain how mammals keep their internal clocks in synch with the sun, according to a paper in this week's Proceedings of the National Academy of Science. The chemical switch is separate from the one involved in vision, which may explain why blind people who lack vision proteins can still maintain a normal biological day-night cycle.

Researchers know that proteins in the eye transmit visual signals to the brain. For many years, these same proteins were thought to keep the daily clock running on time, since the clock can be reset in response to light. However, mice that lack all vision proteins still sleep and wake on schedule, indicating that something else is involved. Aziz Sancar, a biochemist at the University of North Carolina School of Medicine, Chapel Hill, thought that the light-sensing proteins Cryptochrome 1 and 2 (CRY1 and CRY2), which he had recently found in humans, might be involved.

Sancar and his team looked for bits of CRY1 and CRY2 messenger RNA--a chemical indicating that cells are making the protein specified by the gene--in the mice. They found high concentrations of both RNAs in a retinal layer containing neurons that connect to the suprachiasmatic nucleus, a brain region known to be important in the circadian rhythm. That placement makes the proteins good candidates for controlling the mammalian master clock, Sancar says. The group also found low levels of the proteins in tissues throughout the mouse body, supporting the theory that "each organ may have its own clock that might be coordinated with the main clock in the brain," Sancar says.

The work is "incredibly thought-provoking," says Steve Kay, a cell biologist at Scripps Research Institute in La Jolla, California. It doesn't prove that CRY proteins control the circadian clock, but "it lays the groundwork to ask that question," he says. The next step would be to make a mouse without the genes and see if that throws a wrench in the clockworks.

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