Small worm yields big clue on muscle receptor action

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Small worm yields big clue on muscle receptor action

27 Jul 2005 http://www.medicalnewstoday.com/medicalnews.php?

newsid=28101

Researchers at the University of Illinois at Chicago have identified

an elusive subunit of a neurotransmitter receptor found in both

humans and the much-studied laboratory nematode C. elegans which may

open new pathways of research on muscle function.

The neurotransmitter acetylcholine binds to two different nicotinic

receptors at the nematode's neuromuscular junctions, causing them to

contract. Previously, researchers knew the subunit composition only

of the levamisole-sensitive acetylcholine receptors. In the second,

levamisole-insensitive acetylcholine receptors, a subunit called

acetylcholine receptor 16, or ACR-16, has now been identified as

necessary for this receptor's contribution to muscle contraction.

Janet Richmond, assistant professor of biological sciences at UIC,

along with graduate students Denis Touroutine and Burdina,

reported the findings in the July 22 issue of the Journal of

Biological Chemistry. The research also drew on bioinformatic data

provided by , associate professor of cell and

developmental biology at Vanderbilt University, and work by his

graduate students Fox and Von Stetina.

Richmond has developed a preparation for cutting open the microscopic

nematode to record muscle responses when acetylcholine is applied.

Using this preparation, Richmond was still getting muscle contraction

when acetylcholine was applied to worms lacking any of five receptor

subunits known to be sensitive to levamisole, a chemical that poisons

nematodes. Two additional receptor subunits -- ACR-16 and ACR-8 --

identified using Vanderbilt's data, were found to be likely

candidates for the remaining acetylcholine response. ACR-16 was

singled out as the key subunit.

" We've shown the ACR-16-containing receptor is present in muscle and

contributes hugely to the synaptic current, " said Richmond.

" Now we can tag this receptor, see if it's localized at the synapse

and start to mutagenize animals to figure out what makes that

receptor stay or make it to the synapse, " she added.

Richmond said the finding might have direct relevance to humans

because the ACR-16 receptor is very similar to the alpha-7 nicotinic

receptor in the human brain.

The research was funded by grants from the National Institutes of

Health.

University of Illinois at Chicago

http://www.uic.edu