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'Cousin' Of Snake Venom Toxin Found In Mice

ily to which the gene belonged. "Nat and I sat down at the computer one day and tried to match lynx1's sequence of amino acids with those of known proteins. We did an exhaustive search of the database utilizing several different algorithms, then suddenly we got a hit," Miwa said. Relatively small but critically important sections within lynx1 matched the amino acid sequence of a snake toxin called alpha-bungarotoxin. This venom is a member of a large family of proteins called Ly-6. With that in mind, Heintz and Miwa named their gene "lynx," for Ly-6 neurotoxin.

"At that point we realized the potential significance of lynx1," Miwa said. "Bungarotoxin was known to bind to acetylcholine receptors, so if lynx1 could bind to these receptors too, it might be important for brain signaling."

Ines Ibanez-Tallon, an HHMI associate in Heintz's lab, localized the nerve cell receptors with which lynx1 interacts, and showed that the distribution of these receptors is similar to that of acetylcholine receptors in the cerebellum, a region of the brain involved in controlling motion and motor learning.

Additional collaborators in Lorna Role's laboratory at Columbia University tested lynx1's effect on frog eggs (or oocytes) that had been injected with acetylcholine receptors. Miwa said the eggs' acetylcholine response was 30 percent larger after bathing them with lynx1, suggesting that lynx1 might enhance the action of acetylcholine. By contrast, its cousin, alpha-bungarotoxin, interferes with acetylcholine's activity. But many drugs that affect the brain have been found to generate effects opposite to those of similar substances produced by brain tissue, Heintz said.

Acetylcholine receptors are thought to be involved in memory and in the pathogenesis of Alzheimer's disease, where loss of inputs from acetylcholine neurons is a hallmark of the disease. "If lynx1 acts in the whole animal like it does in cells, then the structure of the p
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
28-May-1999


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