Using mutations of a nematode species as a model system, Neuroscience Research Institute at the National Institute of Advanced Industrial Science and Technology (AIST), an independent administrative institution, has succeeded in identifying a novel gene and elucidating its signal-regulation mechanism, providing a key to understanding how neural activity is regulated by muscle cells. The results of this research are expected to be of major import in advancing our understanding of symptoms of myasthenia gravis and similar disorders in humans. This research has been published in the January 17, 2002 issue of the journal Neuron.

Nerves regulate the activities of muscles and internal organs, transmitting critical information needed for an animal’s vitality. Although this type of regulation, known as "anterograde signaling," is commonly thought of as being unidirectional, muscles and internal organs are also known to exhibit a phenomenon called "retrograde signaling" (Fig. 1); this retrograde signaling, considered a feedback mechanism directed from the muscles and internal organs to the nerves, is one crucial mechanism in regulating nerve activity. Furthermore, retrograde signaling affects not only the peripheral nervous system, but is also known to play an extremely important role in plasticity (memory and learning) of the central nervous system, making clarification of this mechanism a highly important research topic in neuroscience.

Many aspects of the mechanism by which retrograde signals are secreted from human muscle and other postsynaptic cells remain unclear. Using a type of nematode as a model system, Molecular Neurobiology Group at Neuroscience Research Institute AIST succeeded in identifying a gene regulating retrograde nerve signals and further clarified the signal release mechanism. The research team, following clues provided in mutations caused by abnormal neural transmissions in the nematodes studied, identified the gene responsible through the utilization of gene transfer techniques used in treating the nematode genes. The mechanism of this gene, called "AEX-1," works by causing a signal to be secreted by muscles and internal organs (Fig. 2). For the first time ever, it has been shown that release of this signal to the nerve cell alters localization of the protein "UNC-13" regulating anterograde signaling at the periphery of the nerve, thus adjusting the amount of neurotransmitter from the nerve's periphery.

Fig. 1. Bidirectional nerve-muscle communication

Fig. 2. Nerve-muscle communication mechanism revealed