TY - JOUR
T1 - Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier
AU - Eshed, Yael
AU - Feinberg, Konstantin
AU - Poliak, Sebastian
AU - Sabanay, Helena
AU - Sarig-Nadir, Offra
AU - Spiegel, Ivo
AU - Bermingham, John R.
AU - Peles, Elior
N1 - Funding Information:
We would like to thank Peter Brophy, Masayuki Komada, Martin Gurmet, Reuven Agami, and Matt Rasband for their generous gift of different antibodies and plasmids; Peter Maurel and Jim Salzer for their help with the myelinating cultures; and Steve Lambert for critical comments on the manuscript. This work was supported by grants from the National Multiple Sclerosis Society (RG3594-A-4) and the NIH (NINDS grant NS50220). E.P. is Incumbent of the Madeleine Haas Russell Career Development Chair.
PY - 2005/7/21
Y1 - 2005/7/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=22544453872&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2005.06.026
DO - 10.1016/j.neuron.2005.06.026
M3 - Article
C2 - 16039564
AN - SCOPUS:22544453872
SN - 0896-6273
VL - 47
SP - 215
EP - 229
JO - Neuron
JF - Neuron
IS - 2
ER -