Cells on the verge of suicide

By
Tuesday, 12 February, 2002


A developing cell in the human body sits on the edge of death, only if a protein messenger from another cell arrives in time to call off the killing, will the cell then mature into any one of the various types of body cells, such as skin, liver and brain.

For the first time, a Rockefeller University scientist and his colleagues have identified the entire team of molecular messengers responsible for issuing certain brain cells with orders to survive.

"Cell death is important during development and in adulthood because it is a very stringent quality-control mechanism that makes sure there are no unwanted, potentially dangerous cells in the body," says Hermann Steller, Strang Professor at Rockefeller and a Howard Hughes Medical Institute investigator.

"In fact, right now cells in our body are dying at a rate of 100,000 cells per second, while at the same time 100,000 new cells are being born."

The research may one day lead to novel treatments for diseases in which too much or too little cell death occurs: too much cell death is associated with neurodegenerative and muscular diseases such as Alzheimer's, Parkinson's, Huntington's and stroke, while too little leads to the survival of cells with mutations, the hallmark of cancer.

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.

The scientists report that a growth factor called SPITZ binds to its receptor and triggers the activation of what is known as the RAS/MAPK pathway. This pathway, in turn, puts the brakes on Hid, which then prevents the chains on the beastly caspases from falling open, thus averting death.

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