Netrins are a family of signaling proteins involved in developmental processes such as neuronal guidance and angiogenesis. The best characterized netrin, netrin-1, signals through a number of different receptors. When acting as a chemoattractant, netrin-1 primarily signals through the DCC receptor and associated protein tyrosine kinase and MAP kinase signaling pathways. When acting as a chemorepellent, netrin-1 signals through the UNC5 receptor, which involves recruitment of the protein tyrosine phosphatase, SHP2.
While netrins are ubiquitously expressed throughout the animal kingdom, our laboratory was the first to describe a netrin-1 like protein in Tetrahymena. This netrin-1 like protein is secreted from Tetrahymena and acts as a chemorepellent. In our current study, we describe signaling through netrin-1 in this organism. Netrin-1 signaling is inhibited by the tyrosine kinase inhibitor, hypericin, and by the broad-spectrum kinase in hibitor, apigenin, both acting in the micromolar range.. We are conducting further studies to determine whether netrin-1 signaling results in changes to the phosphorylation state of intracellular proteins
