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 into the cell surface at the growth cone. Recent studies have indicated that insulin-like growth factor 1 (IGF-1) has a direct local effect on this process. Now, Santiago Quiroga and colleagues report that IGF-1 regulates axonal membrane expansion through the activation of phosphoinositide 3-kinase (PI3K). The authors 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 blocks IGF-1-stimulated plasmalemmal expansion (see ). Furthermore, IGF-1 stimulation leads to the association of active PI3K with microtubules in the growth cone. Thus, the authors suggest, PI3K and its association with microtubules may play a crucial role in the process of axonal assembly at growth cones.
