Differential expression of proteoglycans at central and peripheral nodes of Ranvier.

The nodes of Ranvier are regularly spaced gaps between myelin sheaths that are markedly enriched in voltage-gated sodium channels and associated proteins. Myelinating glia play a key role in promoting node formation, although the requisite glial signals remain poorly understood. In this study, we have examined the expression of glial proteoglycans in the peripheral and central nodes. We report that the heparan sulfate proteoglycan, syndecan-3, becomes highly enriched with PNS node formation; its ligand, collagen V, is also concentrated at the PNS nodes and at lower levels along the abaxonal membrane. The V1 isoform of versican, a chondroitin sulfate proteoglycan, is also present in the nodal gap. By contrast, CNS nodes are enriched in versican isoform V2, but not syndecan-3. We have examined the molecular composition of the PNS nodes in syndecan-3 knockout mice. Nodal components are normally expressed in mice deficient in syndecan-3, suggesting that it has a nonessential role in the organization of nodes in the adult. These results indicate that the molecular composition and extracellular environment of the PNS and CNS nodes of Ranvier are significantly distinct.

Melendez-Vasquez C ，Carey DJ ，Zanazzi G ，Reizes O ，Maurel P ，Salzer JL ... -  《GLIA》

Syndecan-3 and syndecan-4 are enriched in Schwann cell perinodal processes.

Goutebroze L ，Carnaud M ，Denisenko N ，Boutterin MC ，Girault JA ... -  《BMC NEUROSCIENCE》

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

Martin S ，Levine AK ，Chen ZJ ，Ughrin Y ，Levine JM ... -  《-》

Glial M6B stabilizes the axonal membrane at peripheral nodes of Ranvier.

Glycoprotein M6B and the closely related proteolipid protein regulate oligodendrocyte myelination in the central nervous system, but their role in the peripheral nervous system is less clear. Here we report that M6B is located at nodes of Ranvier in peripheral nerves where it stabilizes the nodal axolemma. We show that M6B is co-localized and associates with gliomedin at Schwann cell microvilli that are attached to the nodes. Developmental analysis of sciatic nerves, as well as of myelinating Schwann cells/dorsal root ganglion neurons cultures, revealed that M6B is already present at heminodes, which are considered the precursors of mature nodes of Ranvier. However, in contrast to gliomedin, which accumulates at heminodes with or prior to Na+ channels, we often detected Na+ channel clusters at heminodes without any associated M6B, indicating that it is not required for initial channel clustering. Consistently, nodal cell adhesion molecules (NF186, NrCAM), ion channels (Nav1.2 and Kv7.2), cytoskeletal proteins (AnkG and βIV spectrin), and microvilli components (pERM, syndecan3, gliomedin), are all present at both heminodes and mature nodes of Ranvier in Gpm6b null mice. Using transmission electron microscopy, we show that the absence of M6B results in progressive appearance of nodal protrusions of the nodal axolemma, that are often accompanied by the presence of enlarged mitochondria. Our results reveal that M6B is a Schwann cell microvilli component that preserves the structural integrity of peripheral nodes of Ranvier.

Bang ML ，Vainshtein A ，Yang HJ ，Eshed-Eisenbach Y ，Devaux J ，Werner HB ，Peles E ... -  《-》

Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system.

Zonta B ，Tait S ，Melrose S ，Anderson H ，Harroch S ，Higginson J ，Sherman DL ，Brophy PJ ... -  《-》