Contactin-1 is a functional receptor for neuroregulatory chondroitin sulfate-E
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Chondroitin sulfate (CS) plays critical roles in central nervous system development and regeneration, and individual modifications of CS form a "sulfation code" that regulates growth factor signaling or neuronal growth. Although we have shown that CS-E polysaccharide, but not CS-A or -C polysaccharide, has an inherent ability to promote neurite outgrowth toward primary neurons, its molecular mechanism remains elusive. Here, we show the involvement of a plasma membrane-tethered cell adhesion molecule, contactin-1 (CNTN-1), in CS-E-mediated neurite extension in a mouse neuroblastoma cell line and primary hippocampal neurons. CS-E, but not CS-A, -C, or heparan sulfate, engaged CNTN-1 with significant affinity and induced intracellular signaling downstream of CNTN-1, indicating that CS-E is a selective ligand for a potential CS receptor, CNTN-1, leading to neurite outgrowth. Our data provide the first evidence that biological functions of CS are exerted through the CS receptor-mediated signaling pathway(s).
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Contactin-1 interacts with CS-E in vitro, but this interaction mainly stimulates neurite outgrowth.
“In vitro experiments show that contactin-1 interacts with CS-E, but the main effects of this interaction is the stimulation of neurite outgrowth (Mikami 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 Mikami et al., 2009
CSPGs, especially their GAG moieties, may inhibit growth by binding to a specific receptor.
“Specifically, CSPGs, and particularly their GAG moieties, may act by i) binding to a specific receptor; ii) blocking the growth-promoting activity of integrins; iii) presenting growth-inhibitory proteins.”
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 Mikami et al., 2009
Known CS/CSPG receptors include contactin-1, RPTPσ, LAR, and NgR1 and NgR3.
“Known CS/CSPG receptors are: contactin-1 (Mikami et al., 2009), receptor protein tyrosine phosphatase sigma (RPTPσ; Shen et al., 2009), leukocyte common antigen-related phosphatase (LAR; Fisher et al., 2011) and Nogo receptor (NgR) 1 and 3 (Dickendesher et al., 2012).”
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 Mikami et al., 2009
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Program Overview * Conference Program * Conference Posters * Conference Abstracts
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- Authors
- Mikami, T., Yasunaga, D., & Kitagawa, H.
- Affiliations
- Kobe Pharmaceutical University (JP)
- Corresponding author
- Kitagawa, Hiroshi
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 284
- Issue
- 7
- Pages
- 4494-4499
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2087612255
- Cited by
- 124
- References
- 29
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 11 · 2021: 4 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 10 · 2016: 9 · 2015: 13 · 2014: 16 · 2013: 11 · 2012: 11
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Private School Promotion Foundation
- Japan Society for the Promotion of Science (19390025, 18790073, 20790080)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- contactin-1, chondroitin sulfate E, neurite outgrowth, adhesion molecules, neural regulation, hippocampal neurons, neuroblastoma cells, intracellular signaling, heparan sulfate
- MeSH terms
- Animals, Cell Membrane, Chondroitin Sulfates, Hippocampus, Cell Adhesion Molecules, Neuronal, Neurites, Receptors, Neurotransmitter, Neurotransmitter Agents, Cell Line, Tumor, Mice, Contactins, Contactin 1
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