During nervous system development, proper neuronal connectivity is achieved through the outgrowth of axons and dendrites at the tips or growth cones of the neurites, a process that involves extensive remodelling of the actin cytoskeleton. Ivan Dikic and co-workers now report that the recruitment of protein tyrosine kinase 2 (Pyk2) and the multifunctional adaptor Cbl to lipid rafts is involved in actin reorganisation in growing rat neuronal PC12 cells (see ). In coprecipitation and co-localisation experiments, they show that Pyk2 and Cbl form a complex through the adaptor protein ArgBP2. Overexpression of these three proteins results in broadened neurite extensions and increased lamellipodia formation in the growth cone, suggesting a functional role for the complex during neurite growth. Additional results indicate that the Pyk2-Cbl complex is translocated to lipid rafts and enriched in PC12 growth cones after growth factor stimulation, and the authors conclude that intact lipid rafts and signals initiated by the Pyk2-Cbl complex are critical for the regulation of actin cytoskeletal changes during neurite growth.
