Small GTPases: Mechanisms linking membrane traffic to cytoskeleton during neuritogenesis

During neurite extension, the protrusive activity of the neuronal growth cone is mediated by the coordination of membrane traffic, adhesion to the cell substrate, and reorganization of the cytoskeleton that includes the dynamic rearrangement of actin filaments at the peripheral region of the growth cone. The small GTPases of the Rho family are important regulators of the actin cytoskeleton (Hall, 1998) and are critical for the regulation of axonal and dendritic extension. In particular, studies in different organisms and studies with primary neurons have shown that Rac acts as a regulator of process outgrowth and axonal guidance (Luo, 2000), by stimulating actin polymerization at the growth cone edge surface. On the other hand, the extension of long axons and branched dendrites requires the addition of membrane to the plasmalemma, to support the extraordinary increase of the neuronal surface occurring during neuritogenesis. Therefore, an important contribution of membrane trafficking to neuritogenesis must be accounted for during neuronal differentiation. Trans-Golgi network-derived constitutive exocytosis and membrane recycling after endocytosis are possible sources of membrane addition to the growing tips of neurites.