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Relative of snake venom toxin may aid in understanding nicotine addiction

er that helps to activate muscles and causes them to contract.

The discovery of lynx1 had potential clinical importance since nicotine is known to increase the level of the neurotransmitter dopamine, which in turn produces pleasurable effects in the brain. Following up on Miwas work, lead author of the Neuron paper, Ins Ibaez-Tallon, used antibodies specific to lynx1 to reveal in mice that the protein was closely associated with the nicotinic acetylcholine receptors in neurons.

Ibaez-Tallon then performed more detailed studies of the function of lynx1 by engineering frog eggs, called oocytes, to produce both lynx1 and nicotinic acetylcholine receptors. By studying the oocytes, Ins found that lynx1 directly modified nicotinic receptors an important finding because physiologists had told us they werent really sure that a membrane-bound molecule like lynx-1 could even access the receptor, said Heintz. That finding really stimulated us to do an in-depth analysis of how lynx1 changed the properties of the receptors. She further showed that lynx1 had a dramatic effect on enhancing desensitization of the receptors to acetylcholine, and it did so by directly binding to the receptors, he said.

Co-author Steven Sine and colleagues at The Mayo Foundation performed electrophysiological studies of the effects of lynx1 in cultured human cells, and discovered that lynx1 affected the electrical conductance of the receptors.

Steves findings revealed that lynx1 modulates this receptor in a different way than other known modulators, said Heintz. Since nicotinic acetylcholine receptors are also expressed on immune cells, the prototoxin family that includes lynx1 might have broad regulatory roles in both the immune and nervous systems, he added.

It will be very interesting to find out if this class of molecules in the nervous system just modulates neurotransmitter receptors, or whether they regulate other cell surface receptors. We really
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
18-Mar-2002


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