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Scientists Find First Protein In Central Nervous System Junctions

St. Louis, Nov. 13 -- Scientists have identified the first protein needed for synapse formation in the central nervous system. Synapses are connections between cells that make the nervous system function.

Due to a bizarre twist of evolution, the protein also appears essential for using a trace element called molybdenum.

When the protein is missing, mice display symptoms of two life-threatening human diseases. In one, stiff baby syndrome, some synapses in the spinal cord fail to function properly. In the other, molybdenum cofactor deficiency, cells can't make proper use of molybdenum.

"This is an amazing illustration of how wacky nature can be," says Joshua R. Sanes, Ph.D., a neurobiology professor at Washington University School of Medicine in St. Louis. One of his postdoctoral fellows, Guoping Feng, Ph.D., and Hartmut Tintrup, a graduate student from Heinrich Betz's lab at the Max-Planck Institute for Brain Research in Frankfurt, Germany, are first authors of the paper, which appears in the Nov. 13 issue of Science.

Betz and colleagues discovered the protein, gephyrin, in 1982, isolating it from the spinal cord and brain. They named it after the Greek word for "bridge" because they thought it might connect nerve cell receptors to the cell's internal skeleton, anchoring them in the right place to receive messages from other nerve cells.

A chemical called glycine delivers these messages at some synapses in the spinal cord, damping the activity of recipient cells. It therefore plays a tug-of-war with other chemicals that stimulate the same nerve cells, keeping those cells in balance. When the nerve cells fail to receive glycine signals, they overreact to positive signals and in turn overstimulate muscles. Strychnine, which is commonly used as a rat poison, induces spastic paralysis by blocking receptors for glycine. People with faulty glycine receptors are extremely sick because of excessive contract
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Contact: Linda Sage
sage@medicine.WUSTL.edu
314-286-0119
Washington University School of Medicine
12-Nov-1998


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