Developmental Cell Article Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis

Neurons establish their unique morphology by elab-orating multiple neurites that subsequently form axons and dendrites. Neurite initiation entails sig-nificant surface area expansion, necessitating addi-tion to the plasma membrane. We report that regu-lated membrane delivery coordinated with the actin cytoskeleton is crucial for neuritogenesis and iden-tify two independent pathways that use distinct exocytic and cytoskeletal machinery to drive neurito-genesis. One pathway uses Ena/VASP-regulated actin dynamics coordinated with VAMP2-mediated exocytosis and involves a novel role for Ena/VASP in exocytosis. A second mechanism occurs in the presence of laminin through integrin-dependent activation of FAK and src and uses coordinated activity of the Arp2/3 complex and VAMP7-mediated exocytosis. We conclude that neuritogenesis can be driven by two distinct pathways that differentially coordinate cytoskeletal dynamics and exocytosis. These regulated changes and coordination of cyto-skeletal and exocytic machinery may be used in other physiological contexts involving cell motility and morphogenesis