Signaling pathways leading to axon outgrowth

We previously discovered that inosine, a naturally occurring molecule that is related to adenosine, stimulates many types of neurons to extend axons. Inosine passes through the cell membrane and activates what appears to be a "master switch" that controls the expression of many genes required for axon growth. Dr. Nina Irwin has now identified the target of inosine’s action as Mst3b. Mst3b is a neuron-specific homolog of a protein kinase that controls budding in yeast. Mst3b is rapidly activated by growth factors, and interference with either its expression or its activity prevents neurons from extending axons. Current research is aimed at understanding the cell signaling pathways that lie upstream and downstream from Mst3b.

mRNA stability

A protein called GAP-43, which Dr. Benowitz and other scientists discovered some years back, is important for axon navigation during development and for the ability of nerve cells to reorganize their connections during learning or after injury. Dr. Nina Irwin investigated the mechanisms that control GAP-43 levels using PC12 cells as a model system. The lab previously found that changes in GAP-43 levels that accompany axon growth are controlled in part by regulating the rate at which the mRNA is degraded in the cell. Dr. Irwin found that a protein called ARPP-19 mediates the control of GAP-43 mRNA stability.