Small worm yields big clue on muscle receptor action

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 Anna Burdina, reported the findings in the July 22 issue of the Journal of Biological Chemistry. The research also drew on bioinformatic data provided by David Miller, associate professor of cell and developmental biology at Vanderbilt University, and work by his graduate students Rebecca Fox and Stephen 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.