ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
An integrin-contactin complex regulates CNS myelination by differential Fyn phosphorylation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 127 citations in OpenAlex.
- Fyn kinase: a key mechanistic regulator and therapeutic target in tauopathy and neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Clemastine alleviates cognitive dysfunction after SAH by targeting neuronal CNTN1 to regulate the ADA-adenosine pathway.Acta pharmacologica Sinica · 2026Article
- Multiple adhesion molecules act together in oligodendrocyte-mediated axonal selection and myelin formation.PLoS biology · 2026Article
- Electrical Forces Improve Memory in Old Age.Reviews of physiology, biochemistry and pharmacology · 2025Review
- Oligodendrocytes: Myelination, Plasticity, and Axonal Support.Cold Spring Harbor perspectives in biology · 2024Review
- Developmental origin of oligodendrocytes determines their function in the adult brain.Nature neuroscience · 2024Article
- Single-cell transcriptome sequencing reveals SPP1-CD44-mediated macrophage-tumor cell interactions drive chemoresistance in TNBC.Journal of cellular and molecular medicine · 2024Article
- Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination.Nature communications · 2024Article
- Cleavage of VAMP2/3 Affects Oligodendrocyte Lineage Development in the Developing Mouse Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Effects of ECM proteins (laminin, fibronectin, and type IV collagen) on the biological behavior of Schwann cells and their roles in the process of remyelination after peripheral nerve injury.Frontiers in bioengineering and biotechnology · 2023Article
- Developmental Cues and Molecular Drivers in Myelinogenesis: Revisiting Early Life to Re-Evaluate the Integrity of CNS Myelin.Current issues in molecular biology · 2022Review
- R-Ras1 and R-Ras2 Expression in Anatomical Regions and Cell Types of the Central Nervous System.International journal of molecular sciences · 2022Article
- Presentation and integration of multiple signals that modulate oligodendrocyte lineage progression and myelination.Frontiers in cellular neuroscience · 2022Review
- Fyn Kinase Activity and Its Role in Neurodegenerative Disease Pathology: a Potential Universal Target?Molecular neurobiology · 2021Review
- Pathway-Focused Profiling of Oligodendrocytes Over-Expressing miR-125a-3p Reveals Alteration of Wnt and Cell-to-Cell Signaling.Cellular and molecular neurobiology · 2021Article
- Review
- The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis.Cellular and molecular life sciences : CMLS · 2020Review
- Missing in Action: Dysfunctional RNA Metabolism in Oligodendroglial Cells as a Contributor to Neurodegenerative Diseases?Neurochemical research · 2020Review
- Article
- Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling.Cell death & disease · 2019Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The understanding of how adhesion molecules mediate the axon-glial interactions in the CNS that ensure target-dependent survival of oligodendrocytes and initiate myelination remains incomplete. Here, we investigate how signals from adhesion molecules can be integrated to regulate these initial steps of myelination. We first demonstrate that the Ig superfamily molecule contactin is associated in oligodendrocytes with integrins, extracellular matrix receptors that regulate target-dependent survival by amplification of growth factor signaling. This amplification is inhibited by small interfering RNA-mediated knockdown of contactin in oligodendrocytes. In contrast, the presence of L1-Fc, the extracellular portion of a contactin ligand expressed on axons, enhanced survival and additionally promoted myelination in cocultures of neurons and oligodendrocytes. We further demonstrate that the signals from contactin and integrin are integrated by differential phosphorylation of the Src family kinase Fyn. Integrin induced dephosphorylation of the inhibitory Tyr-531, whereas contactin increased phosphorylation of both Tyr-531 and the activating Tyr-420. The combined effect is an enhanced activity of Fyn and also a dynamic regulation of the phosphorylation/dephosphorylation balance of Fyn, as required for normal cell adhesion and spreading. We conclude, therefore, that a novel integrin/contactin complex coordinates signals from extracellular matrix and the axonal surface to regulate both oligodendrocyte survival and myelination by controlling Fyn activity.
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