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 ... -  《-》

Long-term maintenance of Na+ channels at nodes of Ranvier depends on glial contact mediated by gliomedin and NrCAM.

Amor V ，Feinberg K ，Eshed-Eisenbach Y ，Vainshtein A ，Frechter S ，Grumet M ，Rosenbluth J ，Peles E ... -  《-》

Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier.

Eshed Y ，Feinberg K ，Poliak S ，Sabanay H ，Sarig-Nadir O ，Spiegel I ，Bermingham JR Jr ，Peles E ... -  《NEURON》

A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier.

Feinberg K ，Eshed-Eisenbach Y ，Frechter S ，Amor V ，Salomon D ，Sabanay H ，Dupree JL ，Grumet M ，Brophy PJ ，Shrager P ，Peles E ... -  《-》

Fibronectin type III-like domains of neurofascin-186 protein mediate gliomedin binding and its clustering at the developing nodes of Ranvier.

Labasque M ，Devaux JJ ，Lévêque C ，Faivre-Sarrailh C ... -  《-》