Figure 4. GDNF modulates Sema3B responsiveness by regulating PlexA1 proteolysis.
As spinal commissural axons are growing toward the midline, calpain cleaves the Sema3B receptor PlexA1 to reduce sensitivity to Sema3B. When these neurons reach the midline, GDNF signals through NCAM and its co-receptor GFRα1 to reduce calpain activity. Sema3B then signals repulsion through Nrp2 and PlexA1.