The Rockefeller University Press

Cell polarization is an essential feature that allows many cell types to fulfill their unique functions. Upon differentiation, po-larized cells establish specialized membrane domains with dis-tinct protein composition. In myelinated axons, such membrane compartmentalization is essential for fast and efficient propaga-tion of action potentials in a saltatory manner. The membrane of these axons is divided into several distinct domains that include (1) the nodes of Ranvier, which are gaps between myelin seg-ments where sodium channels are clustered; (2) the paranodal axoglial junction, where the terminal loops of the myelin attach to the axon; (3) the juxtaparanodal region, where Kv1 potas-sium channels are concentrated; and (4) the internode, which are covered by compact myelin (Fig. 1). In the peripheral ner-vous system (PNS), this intricate axonal organization requires specific intercellular contact sites between the axon and myelina-ting Schwann cells (Poliak and Peles, 2003; Eshed-Eisenbach and Peles, 2013), as well as the formation of membrane diffu-sion barriers that restrict the movement of proteins and lipids in the plasma membrane across different domains (Lasiecka et al., 2009; Katsuki et al., 2011). The main membrane barrier that plays an important role in the assembly of the nodes of Ranvier is present at the paranodal junction (Feinberg et al., 2010; Susuki et al., 2013). These septate-like junctions are composed of axonal (Caspr and contactin) and glial (neurofascin 155-kD isoform) adhesion molecules, and are linked through specific adaptor proteins to the actin–spectrin membrane cytoskeleton (Ogawa et al., 2006; Perkins et al., 2008; Nans et al., 2011). Cytoskeletal components of the paranodal junction include the scaffold protein 4.1B, which is required A membrane barrier important for assembly of the nodes of Ranvier is found at the paranodal junction. This junction is comprised of axonal and glial adhesion molecules linked to the axonal actin–spectrin membrane cytoskeleton through specific adaptors. In this issue, Zhang et al. (2013. J. Cell Biol