Nodes of Ranvier form in association with ezrin-radixin-moesin (ERM)-positive Schwann cell processes

In the adult peripheral nerve, microvillous processes of myelinating Schwan n cells project to the nodes of Ranvier; their composition and physiologic function have not been established. As the ezrinradixin-moesin (ERM) protei ns are expressed in the microvilli of many epithelial cells, we have examin ed the expression and distribution of these proteins in Schwann cells and n eurons in vitro and in vivo. Cultured Schwann cells express high levels of all three proteins and the ezrin-binding protein 50, whereas neurons expres s much lower, although detectable, levels of radixin and moesin. Ezrin is s pecific for Schwann cells. All three ERM proteins are expressed predominant ly at the membrane of cultured Schwann cells, notably in their microvilli. In vivo, the ERM proteins are concentrated strikingly in the nodal processe s of myelinating Schwann cells. Because these processes are devoid of myeli n proteins, they represent a unique compartment of the myelinating Schwann cell. During development, the ERM proteins become concentrated at the ends of Schwann cells before myelin basic protein expression, demonstrating that Schwann cells are polarized longitudinally at the onset of myelination. ER M-positive Schwann cell processes overlie and are associated closely with n ascent nodes of Ranvier, identified by clusters of ankyrin G. Ankyrin accum ulation at the node precedes that of Caspr at the paranodes and therefore d oes not depend on the presence of mature paranodal junctions. These results demonstrate that nodes of Ranvier in the peripheral nervous system form in contact with specialized processes of myelinating Schwann cells that are h ighly enriched in ERM proteins.