Cytoskeletal and signaling mechanisms of neurite formation

The formation of a neurite, the basis for axons and dendrites, begins with the concerted accumulation and organization of actin and microtubules. Whereas much is known about the proteins that play a role in these processes, because they perform similar functions in axon branching and filopodia formation, much remains to be discovered concerning the interaction of these individual cytoskeletal regulators during neurite formation. Here, we review the literature regarding various models of filopodial formation and the way in which proteins that control actin organization and polymerization induce neurite formation. Although several different regulators of actin polymerization are involved in neurite initiation, redundancy occurs between these regulators, as the effects of the loss of a single regulator can be mitigated by the addition of neurite-promoting substrates and proteins. Similar to actin dynamics, both microtubule stabilizing and destabilizing proteins play a role in neurite initiation. Furthermore, interactions between the actin and microtubule cytoskeleton are required for neurite formation. Several lines of evidence indicate that the interactions between these two components of the cytoskeleton are needed for force generation and for the localization of microtubules at sites of nascent neurites. The general theme that emerges is the existence of several central regulatory pathways on which extracellular cues converge to control and organize both actin and microtubules to induce the formation of neurites.