Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan
Open accessAbstract
Perineuronal nets (PNs) in the brains of tenascin-R-deficient ( tn-r −/− ) mice develop in temporal concordance with those of wild-type ( tn-r +/+ ) mice. However, the histological appearance of PNs is abnormal in adult tn-r −/− mice. Here, we investigated whether similar defects are also seen in dissociated and organotypic cultures from hippocampus and forebrain of tn-r −/− mice and whether the structure of PNs could be normalized. In tn-r −/− cultures, accumulations of several extracellular matrix molecules were mostly associated with somata, whereas dendrites were sparsely covered, compared with tn-r +/+ mice. Experiments to normalize the structure of PNs in tn-r −/− organotypic slice cultures by depolarization of neurons, or by co-culturing tn-r +/+ and tn-r −/− brain slices failed to restore a normal PN phenotype. However, formation of dendritic PNs in cultures was improved by the application of tenascin-R protein and rescued by polyclonal antibodies to aggrecan and a bivalent, but not monovalent form of the lectin Wisteria floribunda agglutinin. These results show that tenascin-R and aggrecan are decisive contributors to formation and stabilization of PNs and that tenascin-R may implement these functions by clustering of aggrecan. Proposed approaches for restoration of normal PN structure are noteworthy in the context of PN abnormalities in neurological disorders, such as epilepsy, schizophrenia and addiction.
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Binding of the N-terminal of CSPG to hyaluronan chains is stabilised by Hapln, and the C-terminals of three CSPG molecules link with trimeric tenascin-R.
“While binding of the N-terminal of CSPG to hyaluronan chains is stabilised by Hapln, the C-terminals of three CSPG molecules will link with the trimeric tenascin-R [19–21].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [20]
The Introduction says CSPGs bind hyaluronan through their G1 domains and tenascin-R through other domains. It says tenascin-R can be a dimer or trimer and may cross-link CSPG–hyaluronan complexes; it does not specify that exactly three CSPGs link to a trimer. The paper also does not mention Hapln stabilising the CSPG–hyaluronan bond. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe core structure of PNNs consists of chondroitin sulfate proteoglycans of the lectican family, hyaluronan, tenascins, particularly tenascin-R, and link proteins for stabilization.
“The core structure of PNNs consists of chondroitin sulfate proteoglycans (CSPGs) of the lectican family17,18, hyaluronan19,20, tenascins, particularly tenascin-R (TnR)21,22 and link proteins23,24 for stabilization.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [21]
In hippocampal neurons from TnR-deficient mice, PNN organization around dendrites is modified and can be rescued by adding TnR and aggrecan into the culture medium.
“A recent study concerning hippocampal neurons from TnR-deficient mice reported a modified PNN organization around dendrites that could be rescued by adding TnR and aggrecan into the culture medium21.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [21]
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- Authors
- Morawski, M., Dityatev, A., Hartlage-Rübsamen, M., Blosa, M., Holzer, M., Flach, K., Pavlica, S., Dityateva, G., Grosche, J., Brückner, G., & Schachner, M.
- Affiliations
- Leipzig University (DE)
- Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg - Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
- Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Schachner, Melitta
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2014-10-19
- Volume
- 369
- Issue
- 1654
- Pages
- 20140046
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC4173296
- OpenAlex
- W2096385890
- Cited by
- 100
- References
- 48
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 6
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Qucosa (Saxon State and University Library Dresden) (acceptedVersion, other-oa)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- European Commission
- Deutsche Forschungsgemeinschaft (Mo2249/2-1)
- Freistaat Sachsen
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- tenascin-R, perineuronal nets, aggrecan, extracellular matrix assembly, organotypic slice cultures, hippocampus, forebrain, Wisteria floribunda agglutinin, neuronal depolarization, epilepsy, schizophrenia, addiction
- MeSH terms
- Animals, Extracellular Matrix, Oligodendroglia, Mice, Knockout, Cell Culture Techniques, Tenascin, Mice, Aggrecans
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