Secreted gliomedin is a perinodal matrix component of peripheral nerves.
The interaction between gliomedin and the axonodal cell adhesion molecules (CAMs) neurofascin and NrCAM induces the clustering of Na(+) channels at the nodes of Ranvier. We define new interactions of gliomedin that are essential for its clustering activity. We show that gliomedin exists as both transmembrane and secreted forms that are generated by proteolytic cleavage of the protein, and that only the latter is detected at the nodes of Ranvier. The secreted extracellular domain of gliomedin binds to Schwann cells and is incorporated into the extracellular matrix (ECM) in a heparin-dependent manner, suggesting the involvement of heparan sulfate proteoglycans (HSPGs). Furthermore, we show that the N-terminal region of gliomedin serves as an oligomerization domain that mediates self-association of the molecule, which is required for its binding to neurofascin and NrCAM. Our results indicate that the deposition of gliomedin multimers at the nodal gap by binding to HSPGs facilitates the clustering of the axonodal CAMs and Na(+) channels.
Eshed
Yael
Y
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Feinberg
Konstantin
K
Carey
David J
DJ
Peles
Elior
E
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D020836:Protein Structure, Quaternary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011901:Ranvier's Nodes / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D019812:Heparan Sulfate Proteoglycans; D009414:Nerve Growth Factors; D015222:Sodium Channels; C504359:gliomedin, rat; D006493:Heparin