A molecular view on paranodal junctions of myelinated fibers

The axoglial paranodal junctions, flanking the Ranvier nodes, are specialized adhesion sites between the axolemma and myelinating glial cells. Unraveling the molecular composition of paranodal junctions is crucial for understanding the mechanisms involved in the regulation of myelination, and positioning and segregation of the voltage-gated Na+ and K+ channels, essential for the generation and conduction of action potentials. Paranodin/Caspr was the first neuronal transmembrane glycoprotein identified at the paranodal junctions. Paranodin/Caspr is associated on the axonal membrane with contactin/F3, a glycosylphosphatidylinositol-anchored protein, essential for its correct targeting. The extra and intracellular regions of paranodin encompass multiple domains which can be involved in protein-protein interactions with other axonal proteins and glial proteins. Thus, paranodin plays a central role in the assembly of multiprotein complexes necessary for the formation and maintenance of paranodal junctions.