Regulation of membrane expansion at the nerve growth cone

S. QUIROGA

Carlos Paz, Córdoba, Argentina

Workshop; International Workshop on Membrane Trafficking; 2005

REGULATION OF MEMBRANE EXPANSION AT THE NERVE GROWTH CONE. S. Quiroga, Dpto. de Química Biológica y CIQUIBIC-CONICET, Fac. de Ciencias Químicas, Universidad Nacional de Córdoba. During brain development, axons are constructed from structural elements shipped into the nerve growth cone from the cell body. One important component of axonal growth is membrane expansion, which occurs through the exocytic incorporation of plasmalemmal precursor vesicles (PPVs) into the cell surface at the growth cone. Our results indicate that insulin-like growth factor 1 (IGF-1), but not other growth factors such as BDNF, has a direct stimulating local effect on this process. Moreover, IGF-1 regulates axonal membrane expansion through the activation of phosphatidylinositol 3-kinase (PI3K). Our results show that IGF-1 rapidly stimulates the insulin receptor substrate (IRS)/PI3K/Akt signalling pathway in isolated growth cones and hippocampal neurons in culture and that inhibition of this signalling pathway by specific inhibitors such as Wortmannin or LY294002 blocks IGF-1-stimulated plasmalemmal expansion. Furthermore, IGF-1 stimulation leads to the association of active PI3K predominantly with microtubules in the growth cone. Thus, the IGF-1-activated IRS/PI3K/Akt pathway may play a critical role in membrane assembly at the axonal growth cone.