The axonal membrane protein Caspr, a homologue of neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination
Open accessAbstract
We have investigated the potential role of contactin and contactin-associated protein (Caspr) in the axonal–glial interactions of myelination. In the nervous system, contactin is expressed by neurons, oligodendrocytes, and their progenitors, but not by Schwann cells. Expression of Caspr, a homologue of Neurexin IV, is restricted to neurons. Both contactin and Caspr are uniformly expressed at high levels on the surface of unensheathed neurites and are downregulated during myelination in vitro and in vivo. Contactin is downregulated along the entire myelinated nerve fiber. In contrast, Caspr expression initially remains elevated along segments of neurites associated with nascent myelin sheaths. With further maturation, Caspr is downregulated in the internode and becomes strikingly concentrated in the paranodal regions of the axon, suggesting that it redistributes from the internode to these sites. Caspr expression is similarly restricted to the paranodes of mature myelinated axons in the peripheral and central nervous systems; it is more diffusely and persistently expressed in gray matter and on unmyelinated axons. Immunoelectron microscopy demonstrated that Caspr is localized to the septate-like junctions that form between axons and the paranodal loops of myelinating cells. Caspr is poorly extracted by nonionic detergents, suggesting that it is associated with the axon cytoskeleton at these junctions. These results indicate that contactin and Caspr function independently during myelination and that their expression is regulated by glial ensheathment. They strongly implicate Caspr as a major transmembrane component of the paranodal junctions, whose molecular composition has previously been unknown, and suggest its role in the reciprocal signaling between axons and glia.
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Healthy, myelinated axons contain organized clusters of proteins within and surrounding the node of Ranvier, including Caspr in the paranode and Kv1.2 in the juxtaparanode.
“Healthy, myelinated axons contain organized clusters of proteins within and surrounding the node of Ranvier, which includes contactin associated protein (Caspr) in the paranode and the potassium voltage-gated ion channel, Kv1.2, in the juxtaparanode [60–62].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [60]
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“Blots were prehybridized, hybridized, and washed using standard techniques; the final stringency of the wash was 0.2 3 SSC at 65 8 C for 30 min. cDNAs used as probes included an z 500-bp fragment to rat Caspr and an z 1.5-kb fragment to human contactin as described (Peles et al., 1997 b ).”
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- Authors
- Einheber, S., Zanazzi, G., Ching, W., Scherer, S., Milner, T. A., Peles, E., & Salzer, J. L.
- Affiliations
- Cornell University (US)
- Corresponding author
- Peles, Elior
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 1997-12-15
- Volume
- 139
- Issue
- 6
- Pages
- 1495-1506
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2132621
- OpenAlex
- W2113519237
- Cited by
- 369
- References
- 1
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 10 · 2021: 10 · 2020: 7 · 2019: 13 · 2018: 10 · 2017: 11 · 2016: 7 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 14
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- York University
- National Institutes of Health (5p01ns033165-05, NS 33165, HL18974)
- National Heart, Lung, and Blood Institute (HL-18974, P01HL018974)
- National Institute on Drug Abuse (R01DA008259)
- National Institute of General Medical Sciences (T32GM007308)
- National Institute of Neurological Disorders and Stroke (NS 33165, R01NS026001, NS 26001)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Caspr, contactin, myelination, paranodal junctions, axon-glia interaction, oligodendrocytes, Schwann cells, axon cytoskeleton, myelin sheath, internodes
- MeSH terms
- Animals, Axons, Embryo, Mammalian, Ganglia, Spinal, Membrane Glycoproteins, Myelin Sheath, Nerve Fibers, Nerve Fibers, Myelinated, Nerve Tissue Proteins, Neuroglia, Neurons, Oligodendroglia, Receptors, Cell Surface, Schwann Cells, Signal Transduction, Down-Regulation, Cell Adhesion Molecules, Neuronal, Microscopy, Immunoelectron, Neurites, Coculture Techniques, Rats, Contactins
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