Model of Trio regulation by Hsc70 during netrin-1/DCC signaling. Netrin-1/DCC engagement results in recruitment of Trio and Hsc70 to DCC signaling complexes (a). Hsc70 chaperone activity is required for netrin-1–induced activation of Rac1 (b), surface DCC enrichment at the growth cone plasma membrane (c), and axon outgrowth and guidance downstream of netrin-1 (d). Therefore, we propose that Hsc70-mediated regulation of Trio is essential for the stability of the DCC/Trio signaling complex at the cell surface of growth cones to mediate netrin-1–induced cortical axon outgrowth and guidance.