Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system
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Rapid nerve impulse conduction in myelinated axons requires the concentration of voltage-gated sodium channels at nodes of Ranvier. Myelin-forming oligodendrocytes in the central nervous system (CNS) induce the clustering of sodium channels into nodal complexes flanked by paranodal axoglial junctions. However, the molecular mechanisms for nodal complex assembly in the CNS are unknown. Two isoforms of Neurofascin, neuronal Nfasc186 and glial Nfasc155, are components of the nodal and paranodal complexes, respectively. Neurofascin-null mice have disrupted nodal and paranodal complexes. We show that transgenic Nfasc186 can rescue the nodal complex when expressed in Nfasc−/− mice in the absence of the Nfasc155–Caspr–Contactin adhesion complex. Reconstitution of the axoglial adhesion complex by expressing transgenic Nfasc155 in oligodendrocytes also rescues the nodal complex independently of Nfasc186. Furthermore, the Nfasc155 adhesion complex has an additional function in promoting the migration of myelinating processes along CNS axons. We propose that glial and neuronal Neurofascins have distinct functions in the assembly of the CNS node of Ranvier.
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Nfasc and Sgce are differentially spliced in neurons and glia, and this is confirmed in our splicing database.
“Two particularly interesting examples include the differential expression of neuronal and glial isoforms of Nfasc and Sgce genes (Zonta et al., 2008;Ritz et al., 2011), both of which are confirmed in our splicing database, among others.”
From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Zonta et al., 2008
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Peles, E., Nativ, M., Lustig, M., Grumet, M., Schilling, J., Martinez, R., Plowman, G. D., & Schlessinger, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.5.978 · Cited by 400 · cited 1× · see citing works
“…between the glial isoform of Neurofascin, Nfasc155, and the axonal proteins Caspr (also known as Paranodin) and Contactin ( Menegoz et al., 1997 ; Peles et al., 1997 ; Tait et al., 2000 ; Bhat et al., 2001 ; Boyle et al., 2001 ; Kazarinova-Noyes et al., 2001 ; Charles et al., 2002 ; Sherman and…”
BackgroundDependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS
Rasband, M. N., Peles, E., Trimmer, J. S., Levinson, S. R., Lux, S. E., & Shrager, P. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-17-07516.1999 · Cited by 325 · see citing works
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, J. R., & Peles, E. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.026 · Cited by 321 · see citing works
Scotland, P., Zhou, D., Benveniste, H., & Bennett, V. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.5.1305 · Cited by 185 · see citing works
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Research works printed but not linked: 48
- Arroyo, E.J., T. Xu, J. Grinspan, S. Lambert, S.R. Levinson, P.J. Brophy, E. Peles, and S.S. Scherer. 2002. Genetic dysmyelination alters the molecular architecture of the nodal region. J. Neurosci. 22: 1726–1737. 11880502 PMC6758867
- Bennett, V., and S. Lambert. 1999. Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels. J. Neurocytol. 28: 303–318. 10739573
- Berghs, S., D. Aggujaro, R. Dirkx Jr., E. Maksimova, P. Stabach, J.M. Hermel, J.P. Zhang, W. Philbrick, V. Slepnev, T. Ort, and M. Solimena. 2000. βIV spectrin, a new spectrin localized at axon initial segments and nodes of Ranvier in the central and peripheral nervous system. J. Cell Biol. 151: 985–1002. 11086001 PMC2174349
- Bhat, M.A., J.C. Rios, Y. Lu, G.P. Garcia-Fresco, W. Ching, M. St Martin, J. Li, S. Einheber, M. Chesler, J. Rosenbluth, et al. 2001. Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin. Neuron. 30: 369–383. 11395000
- Boiko, T., M.N. Rasband, S.R. Levinson, J.H. Caldwell, G. Mandel, J.S. Trimmer, and G. Matthews. 2001. Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron. 30: 91–104. 11343647
- Boyle, M.E., E.O. Berglund, K.K. Murai, L. Weber, E. Peles, and B. Ranscht. 2001. Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve. Neuron. 30: 385–397. 11395001
- Charles, P., S. Tait, C. Faivre-Sarrailh, G. Barbin, F. Gunn-Moore, N. Denisenko-Nehrbass, A.M. Guennoc, J.A. Girault, P.J. Brophy, and C. Lubetzki. 2002. Neurofascin is a glial receptor for the paranodin/Caspr-contactin axonal complex at the axoglial junction. Curr. Biol. 12: 217–220. 11839274
- Court, F.A., D.L. Sherman, T. Pratt, E.M. Garry, R.R. Ribchester, D.F. Cottrell, S.M. Fleetwood-Walker, and P.J. Brophy. 2004. Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature. 431: 191–195. 15356632
- Davis, J.Q., S. Lambert, and V. Bennett. 1996. Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain−) and NrCAM at nodal axon segments. J. Cell Biol. 135: 1355–1367. 8947556 PMC2121080
- Dupree, J.L., J.L. Mason, J.R. Marcus, M. Stull, R. Levinson, G.K. Matsushima, and B. Popko. 2005. Oligodendrocytes assist in the maintenance of sodium channel clusters independent of the myelin sheath. Neuron Glia Biol. 1: 1–14. PMC1397705 18634596
- Dzhashiashvili, Y., Y. Zhang, J. Galinska, I. Lam, M. Grumet, and J.L. Salzer. 2007. Nodes of Ranvier and axon initial segments are ankyrin G–dependent domains that assemble by distinct mechanisms. J. Cell Biol. 177: 857–870. 17548513 PMC2064285
- Eshed, Y., K. Feinberg, D.J. Carey, and E. Peles. 2007. Secreted gliomedin is a perinodal matrix component of peripheral nerves. J. Cell Biol. 177: 551–562. 17485493 PMC2064815
- Fraher, J.P. 1978. Quantitative studies on the maturation of central and peripheral parts of individual ventral motoneuron axons. II. Internodal length. J. Anat. 127: 1–15. 701187 PMC1235639
- Gillespie, C.S., D.L. Sherman, S.M. Fleetwood-Walker, D.F. Cottrell, S. Tait, E.M. Garry, V.C. Wallace, J. Ure, I.R. Griffiths, A. Smith, and P.J. Brophy. 2000. Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice. Neuron. 26: 523–531. 10839370
- Gollan, L., H. Sabanay, S. Poliak, E.O. Berglund, B. Ranscht, and E. Peles. 2002. Retention of a cell adhesion complex at the paranodal junction requires the cytoplasmic region of Caspr. J. Cell Biol. 157: 1247–1256. 12082082 PMC2173544
- Gollan, L., D. Salomon, J.L. Salzer, and E. Peles. 2003. Caspr regulates the processing of contactin and inhibits its binding to neurofascin. J. Cell Biol. 163: 1213–1218. 14676309 PMC2173730
- Gow, A., C.M. Southwood, J.S. Li, M. Pariali, G.P. Riordan, S.E. Brodie, J. Danias, J.M. Bronstein, B. Kachar, and R.A. Lazzarini. 1999. CNS myelin and sertoli cell tight junction strands are absent in Osp/claudin-11 null mice. Cell. 99: 649–659. 10612400
- Howell, O.W., A. Palser, A. Polito, S. Melrose, B. Zonta, C. Scheiermann, A.J. Vora, P.J. Brophy, and R. Reynolds. 2006. Disruption of neurofascin localization reveals early changes preceding demyelination and remyelination in multiple sclerosis. Brain. 129: 3173–3185. 17041241
- Ishibashi, T., J.L. Dupree, K. Ikenaka, Y. Hirahara, K. Honke, E. Peles, B. Popko, K. Suzuki, H. Nishino, and H. Baba. 2002. A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation. J. Neurosci. 22: 6507–6514. 12151530 PMC6758132
- Jenkins, S.M., and V. Bennett. 2002. Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion. Proc. Natl. Acad. Sci. USA. 99: 2303–2308. 11842202 PMC122360
- Jessen, K.R., and R. Mirsky. 2005. The origin and development of glial cells in peripheral nerves. Nat. Rev. Neurosci. 6: 671–682. 16136171
- Kaplan, M.R., A. Meyer-Franke, S. Lambert, V. Bennett, I.D. Duncan, S.R. Levinson, and B.A. Barres. 1997. Induction of sodium channel clustering by oligodendrocytes. Nature. 386: 724–728. 9109490
- Kaplan, M.R., M.H. Cho, E.M. Ullian, L.L. Isom, S.R. Levinson, and B.A. Barres. 2001. Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier. Neuron. 30: 105–119. 11343648
- Kazarinova-Noyes, K., J.D. Malhotra, D.P. McEwen, L.N. Mattei, E.O. Berglund, B. Ranscht, S.R. Levinson, M. Schachner, P. Shrager, L.L. Isom, and Z.C. Xiao. 2001. Contactin associates with Na+ channels and increases their functional expression. J. Neurosci. 21: 7517–7525. 11567041 PMC6762905
- Kim, H.J., A.B. DiBernardo, J.A. Sloane, M.N. Rasband, D. Solomon, B. Kosaras, S.P. Kwak, and T.K. Vartanian. 2006. WAVE1 is required for oligodendrocyte morphogenesis and normal CNS myelination. J. Neurosci. 26: 5849–5859. 16723544 PMC6675261
- Komada, M., and P. Soriano. 2002. βIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J. Cell Biol. 156: 337–348. 11807096 PMC2199236
- Koticha, D., P. Maurel, G. Zanazzi, N. Kane-Goldsmith, S. Basak, J. Babiarz, J. Salzer, and M. Grumet. 2006. Neurofascin interactions play a critical role in clustering sodium channels, ankyrin G and beta IV spectrin at peripheral nodes of Ranvier. Dev. Biol. 293: 1–12. 16566914
- Lambert, S., J.Q. Davis, and V. Bennett. 1997. Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates. J. Neurosci. 17: 7025–7036. 9278538 PMC6573274
- Lustig, M., G. Zanazzi, T. Sakurai, C. Blanco, S.R. Levinson, S. Lambert, M. Grumet, and J.L. Salzer. 2001. Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier. Curr. Biol. 11: 1864–1869. 11728309
- Maertens, B., D. Hopkins, C.W. Franzke, D.R. Keene, L. Bruckner-Tuderman, D.S. Greenspan, and M. Koch. 2007. Cleavage and oligomerization of gliomedin, a transmembrane collagen required for node of Ranvier formation. J. Biol. Chem. 282: 10647–10659. 17293346
- McEwen, D.P., and L.L. Isom. 2004. Heterophilic interactions of sodium channel beta1 subunits with axonal and glial cell adhesion molecules. J. Biol. Chem. 279: 52744–52752. 15466474
- Menegoz, M., P. Gaspar, M. Le Bert, T. Galvez, F. Burgaya, C. Palfrey, P. Ezan, F. Arnos, and J.A. Girault. 1997. Paranodin, a glycoprotein of neuronal paranodal membranes. Neuron. 19: 319–331. 9292722
- Ogawa, Y., D.P. Schafer, I. Horresh, V. Bar, K. Hales, Y. Yang, K. Susuki, E. Peles, M.C. Stankewich, and M.N. Rasband. 2006. Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton. J. Neurosci. 26: 5230–5239. 16687515 PMC6674250
- Pedraza, L., J.K. Huang, and D.R. Colman. 2001. Organizing principles of the axoglial apparatus. Neuron. 30: 335–344. 11394997
- Poliak, S., and E. Peles. 2003. The local differentiation of myelinated axons at nodes of Ranvier. Nat. Rev. Neurosci. 4: 968–980. 14682359
- Ramon y Cajal, S. 1909. Histologie du Systeme Nerveux de l'Homme et des Vertebris. Vol. 1. Maloine, Paris. 986 pp.
- Rasband, M.N., C.M. Taylor, and R. Bansal. 2003. Paranodal transverse bands are required for maintenance but not initiation of Nav1.6 sodium channel clustering in CNS optic nerve axons. Glia. 44: 173–182. 14515333
- Ratcliffe, C.F., R.E. Westenbroek, R. Curtis, and W.A. Catterall. 2001. Sodium channel β1 and β3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain. J. Cell Biol. 154: 427–434. 11470829 PMC2150779
- Rios, J.C., M. Rubin, M. St Martin, R.T. Downey, S. Einheber, J. Rosenbluth, S.R. Levinson, M. Bhat, and J.L. Salzer. 2003. Paranodal interactions regulate expression of sodium channel subtypes and provide a diffusion barrier for the node of Ranvier. J. Neurosci. 23: 7001–7011. 12904461 PMC6740666
- Salzer, J.L. 2003. Polarized domains of myelinated axons. Neuron. 40: 297–318. 14556710
- Schafer, D.P., R. Bansal, K.L. Hedstrom, S.E. Pfeiffer, and M.N. Rasband. 2004. Does paranode formation and maintenance require partitioning of neurofascin 155 into lipid rafts? J. Neurosci. 24: 3176–3185. 15056697 PMC6730037
- Sherman, D.L., and P.J. Brophy. 2005. Mechanisms of axon ensheathment and myelin growth. Nat. Rev. Neurosci. 6: 683–690. 16136172
- Sherman, D.L., S. Tait, S. Melrose, R. Johnson, B. Zonta, F.A. Court, W.B. Macklin, S. Meek, A.J. Smith, D.F. Cottrell, and P.J. Brophy. 2005. Neurofascins are required to establish axonal domains for saltatory conduction. Neuron. 48: 737–742. 16337912
- Tait, S., F. Gunn-Moore, J.M. Collinson, J. Huang, C. Lubetzki, L. Pedraza, D.L. Sherman, D.R. Colman, and P.J. Brophy. 2000. An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. J. Cell Biol. 150: 657–666. 10931875 PMC2175192
- Volkmer, H., R. Leuschner, U. Zacharias, and F.G. Rathjen. 1996. Neurofascin induces neurites by heterophilic interactions with axonal NrCAM while NrCAM requires F11 on the axonal surface to extend neurites. J. Cell Biol. 135: 1059–1069. 8922386 PMC2133392
- Vouyioukiis, D.A., and P.J. Brophy. 1993. Microtubule-associated protein MAP1B expression precedes the morphological differentiation of oligodendrocytes. J. Neurosci. Res. 35: 257–267. 8350387
- Wiggins, R.C., G. Chongjie, C. Delaney, and T. Samorajski. 1988. Development of axonal-oligodendroglial relationships and junctions during myelination of the optic nerve. Int. J. Dev. Neurosci. 6: 233–243. 3213582
- Yang, Y., S. Lacas-Gervais, D.K. Morest, M. Solimena, and M.N. Rasband. 2004. BetaIV spectrins are essential for membrane stability and the molecular organization of nodes of Ranvier. J. Neurosci. 24: 7230–7240. 15317849 PMC6729762
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“Two particularly interesting examples include the differential expression of neuronal and glial isoforms of Nfasc and Sgce genes (Zonta et al., 2008; Ritz et al., 2011), both of which are confirmed in our splicing database, among others.”
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- Authors
- Zonta, B., Tait, S., Melrose, S., Anderson, H., Harroch, S., Higginson, J., Sherman, D. L., & Brophy, P. J.
- Affiliations
- University of Edinburgh (GB)
- Institut Pasteur (FR)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2008-06-23
- Volume
- 181
- Issue
- 7
- Pages
- 1169-1177
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2442198
- OpenAlex
- W2007023132
- Cited by
- 188
- References
- 4
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 18 · 2019: 13 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 13 · 2014: 14 · 2013: 17 · 2012: 12
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, other-oa)
- Funders
- Wellcome Trust
- Multiple Sclerosis Society
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- neurofascin, nodes of Ranvier, voltage-gated sodium channels, oligodendrocytes, myelination, Caspr, contactin, myelinated axons, central nervous system
- MeSH terms
- Animals, Cell Adhesion, Cell Movement, Central Nervous System, Mice, Inbred C57BL, Myelin Sheath, Nerve Growth Factors, Neuroglia, Neurons, Oligodendroglia, Phenotype, Ranvier's Nodes, Sodium Channels, Cell Adhesion Molecules, Cell Adhesion Molecules, Neuronal, Protein Isoforms, Mutant Proteins, Mice, Contactins
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