Gliomedin Mediates Schwann Cell-Axon Interaction and the Molecular Assembly of the Nodes of Ranvier

Abstract

Accumulation of Na(+) channels at the nodes of Ranvier is a prerequisite for saltatory conduction. In peripheral nerves, clustering of these channels along the axolemma is regulated by myelinating Schwann cells through a yet unknown mechanism. We report the identification of gliomedin, a glial ligand for neurofascin and NrCAM, two axonal immunoglobulin cell adhesion molecules that are associated with Na+ channels at the nodes of Ranvier. Gliomedin is expressed by myelinating Schwann cells and accumulates at the edges of each myelin segment during development, where it aligns with the forming nodes. Eliminating the expression of gliomedin by RNAi, or the addition of a soluble extracellular domain of neurofascin to myelinating cultures, which caused the redistribution of gliomedin along the internodes, abolished node formation. Furthermore, a soluble gliomedin induced nodal-like clusters of Na+ channels in the absence of Schwann cells. We propose that gliomedin provides a glial cue for the formation of peripheral nodes of Ranvier.

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“…Recent data suggest that some olfactomedin-domain containing proteins may interact with membranebound proteins located at the cell surface. For example, gliomedin, a glial ligand for neurofascin and NrCAM, two axonal IgCAMs that are present at the nodes of Ranvier, interacts specifically with these two proteins but not with several related IgCAMs [10]. hGC-1, also known as GW112, OLFM4, and hOlfD, may interact with cell surface lectins and cadherin [31].…”

“…The olfactomedin domain is the most conserved part of the protein molecules and appears to be critical for interaction with other proteins. The olfactomedin domain of gliomedin, is essential for the interaction with neurofascin and NrCAM [10]. Olfactomedin domain of amassin is responsible for coelomocyte-binding activity [41].…”

“…Some of the olfactomedin domain-containing proteins are membrane proteins. For example, gliomedin is a type II transmembrane protein containing the olfactomedin domain in the carboxy-terminal extracellular region [10]. Latrophilins are calcium-independent, seven-transmembrane receptors for latrotoxin (CIRL1-CIRL3) with a large N-terminal extracellular part containing the olfactomedin domain [11][12][13][14][15].…”

“…Xenopus tiarin may participate in the specification of the dorsal neural tube [9]. Gliomedin may mediate Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier [10]. Sea urchin amassin mediates the massive intercellular adhesion of coelomocytes, the immune cells contained in the coelomic cavity [5].…”

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“…Gliomedin, a recently identified transmembrane collagen containing an olfactomedin domain, is essential to formation of the nodes of Ranvier (Eshed et al, 2005). Expressed on the surface of Schwann cells, gliomedin serves as a ligand for the neuronal Immunoglobulin Cell Adhesion Molecules (IgCAMs) Nr-CAM and neurofascin (Eshed, et al, 2005).…”