AU researcher finds unknown function for well-known protein

It is a well-known protein thought to be important for how nerves form connections to muscles. But an Augusta University researcher found it actually has a previously unknown function, one that seems also to be crucial for making that connection, that could lead to new insights into how those connections fail in disease.


Dr. Lin Mei, the chairman of the Department of Neuroscience and Regenerative Medicine, recently published his findings in the journal Neuron. He was looking at the neuromuscular junction, the connection between nerve and muscle that allows a nerve to signal the muscle. Part of that connection depends on the presence of clusters of receptors for the neurotransmitter that the nerve is releasing to catch that signal.


“If you don’t have enough receptors or they are not clustered, then you can imagine neurotransmission would be a problem,” Mei said.

Those receptors are anchored into place by something called a scaffold protein, in this case called rapsyn, Mei said.

“Exactly how rapsyn functions was not known except that people believed they were adaptive proteins or scaffold proteins” important for those receptors, he said.

They know the protein is important because when mice are bred not to have it they don’t survive birth because they don’t form neuromuscular junctions and can’t breathe, Mei said. Further research showed that the mice die when only one part of the protein is mutated, he said.

“That gives us a hint that this domain may be critical,” Mei said.

Researchers got another surprise in that the domain acts as an enzyme, a function they did not know it could do, Mei said. Many muscle diseases might come from problems in this neuromuscular junction, and Mei’s lab has been painstakingly establishing which of these proteins is critical to proper function. But how they created the actual connections or assured the presence of the necessary receptors was unknown, Mei said.

”Now we believe we are closing this loop or gap,” he said. “This enzymatic activity may come back and talk to (other critical muscle proteins). We are looking into this.”

When people are studying progressive muscle diseases, they often are focused on finding problems in the muscles themselves, Mei said.

The AU researchers “recognized that people pay too much attention to the muscle weakness, per se, and do not pay attention to how the neuronal signal was transferred to the muscle,” he said. “And whether that (neuromuscular junction) is altered during aging or under disease conditions. I believe this novel finding certainly provides a new target for us to look at. It opens a new avenue.”

Reach Tom Corwin at (706) 823-3213




Sun, 12/17/2017 - 19:16

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