Figure 4. Trio and upstream regulators in axon outgrowth and guidance. (A) Trio mediates Rac1 activation and axon outgrowth and guidance in response to netrin-1 in mammals. Phosphorylation of Trio by the Src-family tyrosine kinase Fyn is essential for Rac1 activation by netrin-1 and for the proper targeting of DCC to the cell surface of growth cones in order to mediate netrin-1-induced cortical axon outgrowth. (B) In C. elegans, UNC-73 acts upstream of UNC-40 (ortholog of DCC) and of SAX-3 (ortholog of Robo) to positively regulate their levels at the cell membrane. UNC-73 cooperates positively with the kinesin-like protein VAB-8 and, in the SAX-3 pathway, negatively with CRML-1, the C. elegans ortholog of CARMIL (capping protein, Arp2/3, and Myosin-I linker), a protein controlling actin dynamics in lamellipodia in mammals.