ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
The cytoskeletal adaptor protein band 4.1B is required for the maintenance of paranodal axoglial septate junctions in myelinated axons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- Neonatal inflammation disrupts a temporally restricted postnatal Numb-enriched microglial state in mice.Nature communications · 2026Article
- Paranodal instability driven by axonal mitochondrial accumulation in ischemic demyelination and cognitive decline.Molecular psychiatry · 2025Article
- Biallelic EPB41L3 variants underlie a developmental disorder with seizures and myelination defects.Brain : a journal of neurology · 2024Article
- A class-specific effect of dysmyelination on the excitability of hippocampal interneurons.eLife · 2023Article
- The Node of Ranvier as an Interface for Axo-Glial Interactions: Perturbation of Axo-Glial Interactions in Various Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Article
- LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period.The Journal of cell biology · 2023Article
- Schwann cell nodal membrane disruption triggers bystander axonal degeneration in a Guillain-Barré syndrome mouse model.The Journal of clinical investigation · 2022Article
- Impact of Neurofascin on Chronic Inflammatory Demyelinating PolyneuropathyFrontiers in molecular neuroscience · 2021Review
- Assembly and Function of the Juxtaparanodal Kv1 Complex in Health and Disease.Life (Basel, Switzerland) · 2020Review
- Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier.PLoS biology · 2020Article
- Accumulation of Neurofascin at Nodes of Ranvier Is Regulated by a Paranodal Switch.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Ablation of cytoskeletal scaffolding proteins, Band 4.1B and Whirlin, leads to cerebellar purkinje axon pathology and motor dysfunction.Journal of neuroscience research · 2019Article
- Selective Axonal Expression of the Kv1 Channel Complex in Pre-myelinated GABAergic Hippocampal Neurons.Frontiers in cellular neuroscience · 2019Article
- The Axonal Cytoskeleton and the Assembly of Nodes of Ranvier.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2018Review
- Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases.Neural regeneration research · 2017Review
- Axonal domain disorganization in Caspr1 and Caspr2 mutant myelinated axons affects neuromuscular junction integrity, leading to muscle atrophy.Journal of neuroscience research · 2017Article
- Assembly of CNS Nodes of Ranvier in Myelinated Nerves Is Promoted by the Axon Cytoskeleton.Current biology : CB · 2017Article
- Mechanisms of sodium channel clustering and its influence on axonal impulse conduction.Cellular and molecular life sciences : CMLS · 2016Review
- Autoimmune antigenic targets at the node of Ranvier in demyelinating disorders.Nature reviews. Neurology · 2015Review
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
Precise targeting and maintenance of axonal domains in myelinated axons is essential for saltatory conduction. Caspr and Caspr2, which localize at paranodal and juxtaparanodal domains, contain binding sites for the cytoskeletal adaptor protein 4.1B. The exact role of 4.1B in the organization and maintenance of axonal domains is still not clear. Here, we report the generation and characterization of 4.1B-null mice. We show that loss of 4.1B in the PNS results in mislocalization of Caspr at paranodes and destabilization of paranodal axoglial septate junctions (AGSJs) as early as postnatal day 30. In the CNS, Caspr localization is progressively disrupted and ultrastructural analysis showed paranodal regions that were completely devoid of AGSJs, with axolemma separated from the myelin loops, and loops coming off the axolemma. Most importantly, our phenotypic analysis of previously generated 4.1B mutants, used in the study by Horresh et al. (2010), showed that Caspr localization was not affected in the PNS, even after 1 year; and 4.1R was neither expressed, nor enriched at the paranodes. Furthermore, ultrastructural analysis of these 4.1B mutants showed destabilization of CNS AGSJs at ∼ 1 year. We also discovered that the 4.1B locus is differentially expressed in the PNS and CNS, and generates multiple splice isoforms in the PNS, suggesting 4.1B may function differently in the PNS versus CNS. Together, our studies provide direct evidence that 4.1B plays a pivotal role in interactions between the paranodal AGSJs and axonal cytoskeleton, and that 4.1B is critically required for long-term maintenance of axonal domains in myelinated axons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.