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Study in Worms Shows How Proteins Work to Dispatch Nerve Signals

Researchers at the University of Utah have unraveled how two proteins¿UNC-13 and syntaxin¿work together to enable nerve cells to communicate. In general, neurons relay messages using chemicals called neurotransmitters. Now Janet Richmond, Robby Weimer and Erik Jorgensen have discovered that UNC-13 primes syntaxin¿much like a crank opening a catapult¿to fire neurotransmitters into the gaps, or synapses, between nerve cells. The finding appears in today's Nature.

The researchers knew that syntaxin comes in two forms. When the protein is unfolded, tiny bubbles filled with neurotransmitters can stick to it, fuse to the inside wall of a nerve cell and then break free into a synapse. When syntaxin is folded, though, the bubbles can't stick to it and the nerve cell can't pass on its signal. Richmond's team suspected that UNC-13 opened syntaxin, thus allowing signals to flow.

To test this theory, they modified the gene encoding syntaxin in a strain of the nematode worm Caenorhabditis elegans so that the protein would remain unfolded. As it turned out, neurotransmitters continued to flow, even when the researchers also knocked out the gene for UNC-13 in these worms. When the scientists eliminated UNC-13 in worms that produced normal syntaxin, however, the flow of neurotransmitters stopped, paralyzing the animals.

The team concluded that UNC-13 does indeed unfold syntaxin and is therefore vital to the dispatch of nerve signals and memory. "It [UNC-13] grabs syntaxin and opens it up like a catapult," Jorgensen says. "The connection between nerve cells stores information and transmits it. What this study has shown is what molecules control the strength of those connections and thus how information is stored and transmitted."

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