Larry Benowitz, PhD

Inosine & Cell Signaling Pathways

Signaling pathways leading to axon outgrowth

We previously discovered that inosine, a naturally occurring molecule derived from adenosine, stimulates several types of neurons to extend axons. Inosine passes through the cell membrane and activates a protein called Mst3b, which appears to be a "master regulator" of the intracellular pathway that controls the growth of axons. A new study by Drs. Nina Irwin, Barbara Lorber and other members of the lab showed that Mst3b regulates the intracellular signaling pathway through which trophic factors lead to the growth of axons. Suppression of Mst3b's expression (using shRNA technology) rendered multiple types of neurons unable to respond to growth factors, whereas a genetically altered form of Mst3b that is always in the active state caused nerve cells to grow axons even when trophic factors were absent. In addition, they showed that Mst3b plays an essential role in the regeneration of injured brain pathways in mature animals.