The ins and outs of polarized axonal domains

Myelinated axons are divided into polarized subdomains including axon initial segments and nodes of Ranvier. These domains initiate and propagate action potentials and regulate the trafficking and localization of somatodendritic and axonal proteins. Formation of axon initial segments and nodes of Ranvier depends on intrinsic (neuronal) and extrinsic (glial) interactions. Several levels of redundancy in both mechanisms and molecules also exist to ensure efficient node formation. Furthermore, the establishment of polarized domains at and near nodes of Ranvier reflects the intrinsic polarity of the myelinating glia responsible for node assembly. Here, we discuss the various polarized domains of myelinated axons, how they are established by both intrinsic and extrinsic interactions, and the polarity of myelinating glia.