Fig. 2.

Trio family proteins respond to axon guidance cues through guidance receptors. Trio family proteins respond to both attractive and repulsive guidance cues, which induces either axon outgrowth or growth cone collapse. (1) In the presence of netrin, the netrin receptor DCC interacts with Trio – it is unknown if this interaction is direct. This interaction results in a Trio GEF1-mediated activation of Rac1, which is necessary for axon outgrowth. (2) Netrin stimulation also induces phosphorylation of Trio at Y2622 by the kinase Fyn (yellow star), which leads to increased surface levels of DCC. While the roles of Trio in pathways (1) and (2) have not been explicitly connected, Trio-dependent stimulation of DCC at the surface (2) likely constitutes a positive feedback loop to amplify more netrin-DCC signaling in (1). (3) In contrast, binding of Slit to the Robo/SAX-3 receptors results in Trio GEF2-mediated RhoA activation, which causes growth cone collapse.