Glial ankyrins facilitate paranodal axoglial junction assembly.

Abstract

Neuron-glia interactions establish functional membrane domains along myelinated axons. These include nodes of Ranvier, paranodal axoglial junctions, and juxtaparanodes. Paranodal junctions are the largest vertebrate junctional adhesion complex, are essential for rapid saltatory conduction, and contribute to assembly and maintenance of nodes. However, the molecular mechanisms underlying paranodal junction assembly are poorly understood. Ankyrins are cytoskeletal scaffolds traditionally associated with Na+ channel clustering in neurons and important for membrane domain establishment and maintenance in many cell types. Here, we show that ankyrinB, expressed by Schwann cells, and ankyrinG, expressed by oligodendrocytes, are highly enriched at the glial side of paranodal junctions where they interact with the essential glial junctional component neurofascin 155. Conditional knockout of ankyrins in oligodendrocytes disrupts paranodal junction assembly and delays nerve conduction during early development in mice. Thus, glial ankyrins function as major scaffolds that facilitate early and efficient paranodal junction assembly in the developing central nervous system.