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Cells on the verge of suicide

equire specific external signals called "survival" factors or "trophic" factors - which are secreted from neighboring cells - to survive. Those that do not receive the trophic signals commit suicide by default. That is, cells have to compete for trophic signals in order to survive.

"This 'social control' theory of cell survival explains why no one cell type outnumbers another," says Steller. "The body has essentially figured out a way to keep its cell numbers in check."

The brain's trophic survival signals work by suppressing a cell's "cell death machinery" - which includes Grim, Reaper and Hid and a family of enzymes called caspases.

"Normally, caspases, which are the key executioners, are locked up by other proteins, which I refer to as the 'brakes on death,'" says Steller, who discovered the Reaper family in 1994.

"But in order to get cells to self-destruct, these brakes have to be released, and that's the job of Reaper, Hid and Grim. Like keys unlocking the door to a dangerous beast restrained behind it, they activate other proteins called caspases to chop up all sorts of proteins, and death ensues."

Although scientists understood the mechanics of this cell suicide process, they did not know how it was suppressed by survival signals; the molecular link between these two crucial life processes remained a black box.

Now, Steller and his colleagues have identified the entire series of proteins that relay a message of survival from a neuron to a glial cell in the fruit fly Drosophila melanogaster. The surviving glial cells are required for proper formation of axons - the long extensions that allow neurons to communicate with other distant cells. According to Steller, there may be other cell death pathways with similar outcomes, but this one is the first to be elucidated in full.

"Although the regulation of cell survival and cell death has been studied intensely, in not one case has the precise, step-by-ste
'"/>

Contact: Whitney Clavin
clavinw@rockefeller.edu
212-327-7250
Rockefeller University
31-Jan-2002


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