Cellular mechanisms of netrin function: Long-range and short-range actions

Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional cues that act as an attra ctant for some cell types and as a repellent for others. Several lines of e vidence suggest that two classes of receptors, the deleted in colorectal ca ncer (DCC) family and the UNC-5 family, mediate the attractant and repellen t response to netrin. Although netrins were first identified as diffusible long-range cues for developing axons, recent findings provide evidence that they also function as short-range cues close to the surface of the cells t hat produce them. This short-range function of netrin contributes to guidin g neurite outgrowth and mediating cell-cell interactions during development and perhaps also in adults.