Versican V2 Assembles the Extracellular Matrix Surrounding the Nodes of Ranvier in the CNS
Open accessAbstract
The CNS-restricted versican splice-variant V2 is a large chondroitin sulfate proteoglycan incorporated in the extracellular matrix surrounding myelinated fibers and particularly accumulating at nodes of Ranvier. In vitro, it is a potent inhibitor of axonal growth and therefore considered to participate in the reduction of structural plasticity connected to myelination. To study the role of versican V2 during postnatal development, we designed a novel isoform-specific gene inactivation approach circumventing early embryonic lethality of the complete knock-out and preventing compensation by the remaining versican splice variants. These mice are viable and fertile; however, they display major molecular alterations at the nodes of Ranvier. While the clustering of nodal sodium channels and paranodal structures appear in versican V2-deficient mice unaffected, the formation of the extracellular matrix surrounding the nodes is largely impaired. The conjoint loss of tenascin-R and phosphacan from the perinodal matrix provide strong evidence that versican V2, possibly controlled by a nodal receptor, organizes the extracellular matrix assembly in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mice deficient for versican, neurocan, or brevican have largely normal PNNs.
“Whereas mice deficient for versican, neurocan, or brevican have largely normal PNNs (Dours--Zimmermann et al., 2009)”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Dours--Zimmermann et al., 2009
The section on effects of the versican V0/V2 knockout reports characteristic perineuronal-net staining in those mice. The Discussion says brevican- and neurocan-knockout mice showed no alterations on histological examination, but does not specifically establish that their perineuronal nets were largely normal. The paper also distinguishes its V0/V2 knockout from a knockout of all versican isoforms, which it says is embryonically lethal; page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe perinodal net, a PNN-like structure, is commonly associated with the node of Ranvier.
“the perinodal-matrix or peridonal net, a PNN-like structure (Dours-Zimmermann et al., 2009; Zimmermann and Dours-Zimmermann, 2008), is commonly associated with the node of Ranvier”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Dours-Zimmermann et al., 2009
The HLT model made from PNN fits the perinodal matrix except that versican V2 is the most common lectican and aggrecan is absent at the node.
“Of particular note is that the HLT model made from PNN fits to this PM except for the differences that vercican V2 is the most common lectican and aggrecan is absent at the node (Bekku et al., 2009;Dours-Zimmermann et al., 2009).”
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 Dours-Zimmermann et al., 2009
The distinctive ECM at the nodes is mainly composed of the lectican family of CSPGs and their binding partners.
“Today we know that this distinctive ECM is mainly composed of lectican family of CSPG and their binding partners (Dours-Zimmermann et al., 2009).”
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 Dours-Zimmermann et al., 2009
Clustering of nodal sodium channels and paranodal structures appear unaffected in both Vcan V0/V2- and Tnr-deficient mice.
“While the clustering of nodal sodium channels and paranodal structures appear unaffected in both Vcan V0/V2-and Tnr-deficient mice, effect on the conduction velocity is different in the three types of mutants (V0/V2-, Tnr-andHapln2/Bral1-deficient mice), probably due to the differences of degree of disturbed ECM assembly (Bekku et al., 2010;Dours-Zimmermann et al., 2009;Weber et al., 1999).”
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 Dours-Zimmermann et al., 2009
Disruption of any single nodal ECM gene does not affect the clustering of nodal Na+ channels.
“Actually, disruption of any single nodal ECM gene does not affect the clustering of nodal Na + channels (Bekku et al., 2010;Dours-Zimmermann et al., 2009;Weber et al., 1999).”
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 Dours-Zimmermann et al., 2009
The effect on conduction velocity differs among Vcan V0/V2-, Tnr-, and Hapln2/Bral1-deficient mice, probably due to differences in the degree of disturbed ECM assembly.
“While the clustering of nodal sodium channels and paranodal structures appear unaffected in both Vcan V0/V2-and Tnr-deficient mice, effect on the conduction velocity is different in the three types of mutants (V0/V2-, Tnr-andHapln2/Bral1-deficient mice), probably due to the differences of degree of disturbed ECM assembly (Bekku et al., 2010;Dours-Zimmermann et al., 2009;Weber et al., 1999).”
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 Dours-Zimmermann et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Extracellular matrix of the central nervous system: from neglect to challenge
Zimmermann, D. R., & Dours-Zimmermann, M. T. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0485-9 · Cited by 465 · see citing works
Self-citationBrückner, G., Brauer, K., Härtig, W., Wolff, J. R., Rickmann, M. J., Derouiche, A., Delpech, B., Girard, N., Oertel, W. H., & Reichenbach, A. (1993) · Glia · doi:10.1002/glia.440080306 · Cited by 358 · 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
Neurofascin assembles a specialized extracellular matrix at the axon initial segment
Hedstrom, K. L., Xu, X., Ogawa, Y., Frischknecht, R., Seidenbecher, C. I., Shrager, P., & Rasband, M. N. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200705119 · Cited by 268 · see citing works
Weber, P., Bartsch, U., Rasband, M. N., Czaniera, R., Lang, Y., Bluethmann, H., Margolis, R. U., Levinson, S. R., Shrager, P., Montag, D., et al. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04245.1999 · Cited by 247 · see citing works
Perineuronal nets potentially protect against oxidative stress
Morawski, M., Brückner, M. K., Riederer, P., Brückner, G., & Arendt, T. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.04.017 · Cited by 246 · see citing works
Neurocan Is Dispensable for Brain Development
Zhou, X.-H., Brakebusch, C., Matthies, H., Oohashi, T., Hirsch, E., Moser, M., Krug, M., Seidenbecher, C. I., Boeckers, T. M., Rauch, U., et al. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.17.5970-5978.2001 · Cited by 206 · see citing works
Self-citationStys, P. K., Ransom, B. R., & Waxman, S. G. (1991) · Brain Research · doi:10.1016/0006-8993(91)91154-s · Cited by 195 · see citing works
A sodium channel signaling complex: modulation by associated receptor protein tyrosine phosphatase β
Ratcliffe, C. F., Qu, Y., McCormick, K. A., Tibbs, V. C., Dixon, J. E., Scheuer, T., & Catterall, W. A. (2000) · Nature Neuroscience · doi:10.1038/74805 · Cited by 182 · see citing works
Day, J. M., Olin, A. I., Murdoch, A. D., Canfield, A., Sasaki, T., Timpl, R., Hardingham, T. E., & Aspberg, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400242200 · Cited by 127 · cited 2× · see citing works
“In addition, the lectin-like element in the C-terminal G3 domain displays in vitro moderate-to-high binding affinities toward tenascin-R (TnR) (Aspberg et al., 1997), tenascin-C (TnC) (Day et al., 2004), and sulfated glycolipids (Miura et al., 1999).”
BackgroundStructural Basis for Interactions between Tenascins and Lectican C-Type Lectin Domains
Lundell, A., Olin, A. I., Mörgelin, M., al-Karadaghi, S., Aspberg, A., & Logan, D. T. (2004) · Structure · doi:10.1016/j.str.2004.05.021 · Cited by 127 · see citing works
Oohashi, T., Hirakawa, S., Bekku, Y., Rauch, U., Zimmermann, D. R., Su, W.-D., Ohtsuka, A., Murakami, T., & Ninomiya, Y. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2001.1061 · Cited by 124 · see citing works
Self-citationBekku, Y., Rauch, U., Ninomiya, Y., & Oohashi, T. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05873.x · Cited by 104 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function
Fawcett, J. W., Oohashi, T., & Pizzorusso, T. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0196-3 · Cited by 589 · see citing works
Extracellular Matrix: Functions in the Nervous System
Barros, C. S., Franco, S. J., & Muller, U. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005108 · Cited by 506 · see citing works
Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity
Sorg, B. A., Berretta, S., Blacktop, J. M., Fawcett, J. W., Kitagawa, H., Kwok, J. C. F., & Miquel, M. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2351-16.2016 · Cited by 454 · see citing works
Three mechanisms assemble central nervous system nodes of Ranvier
Susuki, K., Chang, K.-J., Zollinger, D. R., Liu, Y., Ogawa, Y., Eshed-Eisenbach, Y., Dours-Zimmermann, M. T., Oses-Prieto, J. A., Burlingame, A. L., Seidenbecher, C. I., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.005 · Cited by 186 · see citing works
Self-citationCell adhesion and matricellular support by astrocytes of the tripartite synapse
Hillen, A. E. J., Burbach, J. P. H., & Hol, E. M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.02.002 · Cited by 108 · see citing works
Perineuronal nets and schizophrenia: The importance of neuronal coatings
Bitanihirwe, B. K. Y., & Woo, T.-U. W. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.03.018 · Cited by 95 · see citing works
Bekku, Y., Saito, M., Moser, M., Fuchigami, M., Maehara, A., Nakayama, M., Kusachi, S., Ninomiya, Y., & Oohashi, T. (2012) · Journal of Comparative Neurology · doi:10.1002/cne.23009 · Cited by 65 · see citing works
- Authors
- Dours-Zimmermann, M. T., Maurer, K., Rauch, U., Stoffel, W., Fassler, R., & Zimmermann, D. R.
- Affiliations
- University of Zurich (CH)
- Lund University (SE)
- University of Cologne (DE)
- Corresponding author
- Zimmermann, D. R.
- ORCID
- Rauch, U.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-06-17
- Volume
- 29
- Issue
- 24
- Pages
- 7731-7742
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6665632
- OpenAlex
- W2064482164
- Cited by
- 123
- References
- 13
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 6 · 2021: 7 · 2020: 8 · 2019: 3 · 2018: 10 · 2017: 3 · 2016: 4 · 2015: 11 · 2014: 10 · 2013: 6 · 2012: 7
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Velux Stiftung
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- nodes of Ranvier, extracellular matrix assembly, chondroitin sulfate proteoglycans, myelination, axon growth inhibition, tenascin-R, phosphacan, sodium channel clustering, postnatal development, central nervous system
- MeSH terms
- Action Potentials, Animals, Central Nervous System, Myelin Basic Protein, Extracellular Matrix, Mice, Inbred C57BL, Nerve Tissue Proteins, Neural Conduction, Ranvier's Nodes, Sodium Channels, Cell Adhesion Molecules, Neuronal, Mice, Knockout, Gene Expression Regulation, Developmental, Tenascin, Protein Isoforms, Mice, Kv1.2 Potassium Channel, Versicans, Receptor-Like Protein Tyrosine Phosphatases, Class 5, Contactins, NAV1.6 Voltage-Gated Sodium Channel
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
