Deposition of the NG2 proteoglycan at nodes of Ranvier in the peripheral nervous system

The node of Ranvier is a complex macromolecular assembly of ion channels an d other proteins that is specialized for the rapid propagation of the actio n potential. A full understanding of the processes responsible for the asse mbly and maintenance of the node requires first the identification and char acterization of the proteins found there. Here we show that NG2, a structur ally unique chondroitin sulfate proteoglycan, is a molecular component of t he node of Ranvier in the peripheral nervous system. In adult sciatic nerve , NG2 is (1) associated with thin, elongated fibroblast-like cells, (2) on some but not all basal laminae, and (3) at nodes of Ranvier. At the nodes, NG2 is restricted to the nodal gap and is absent from the paranodal or juxt aparanodal region. In dissociated cell cultures of adult sciatic nerve, per ineurial fibroblasts but not Schwann cells express NG2 on their surfaces. A pproximately 45% of the total NG2 in peripheral nerves is in a soluble, rat her than particulate, subcellular compartment. NG2 is also present in membr ane fractions that also contain high levels of voltage-dependent sodium cha nnels, caspr, and neuron-glia related cell adhesion molecule. These medium- density membranes likely correspond to the nodal and paranodal region of th e axon-Schwann cell unit. These results suggest a model in which perineuria l fibroblasts secrete or shed NG2, which subsequently associates with nodes of Ranvier. The growth-inhibitory and anti-adhesive properties of NG2 may limit the lateral extension of myelinating Schwann cells as nodes mature. N G2 may also participate in the barrier functions of the perineurial linings of the nerve.