Secreted gliomedin is a perinodal matrix component of peripheral nerves
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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.
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Proteolytically cleaved gliomedin is incorporated into the Schwann cell ECM at the nodal gaps.
“Subsequently, proteolytically cleaved glyomedin is incorporated into the Schwann cell ECM at the nodal gaps (Eshed et al., 2007).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Eshed et al., 2007
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Self-citation
- Authors
- Eshed, Y., Feinberg, K., Carey, D. J., & Peles, E.
- Affiliations
- 1Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
- Weizmann Institute of Science (IL)
- Geisinger Medical Center (US)
- Corresponding author
- Peles, Elior
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-05-07
- Volume
- 177
- Issue
- 3
- Pages
- 551-562
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2064815
- OpenAlex
- W2149666315
- Cited by
- 103
- References
- 56
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 9 · 2018: 5 · 2017: 6 · 2016: 3 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 4
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS050220, NS50220)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- nodes of Ranvier, peripheral nerves, Schwann cells, extracellular matrix, heparan sulfate proteoglycans, neurofascin, NrCAM, sodium channel clustering, proteolytic cleavage, oligomerization domain, nodal gap
- MeSH terms
- Animals, Cells, Cultured, Extracellular Matrix, Heparin, Nerve Growth Factors, Protein Processing, Post-Translational, Ranvier's Nodes, Sodium Channels, Cell Adhesion Molecules, Neuronal, Protein Structure, Tertiary, Heparan Sulfate Proteoglycans, Protein Structure, Quaternary, Rats
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