Axon-Glia Interactions and the Domain Organization of Myelinated Axons Requires Neurexin IV/Caspr/Paranodin

Cardiovascular Research Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Neuron (Impact Factor: 15.05). 06/2001; 30(2):369-83. DOI: 10.1016/S0896-6273(01)00294-X
Source: PubMed

ABSTRACT Myelinated fibers are organized into distinct domains that are necessary for saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specialized septate-like junctions with axons. These junctions contain a Drosophila Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of NCP1, normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and K(+) channels are displaced from the juxtaparanodal into the paranodal domains. Loss of NCP1 also results in a severe decrease in peripheral nerve conduction velocity. These results show a critical role for NCP1 in the delineation of specific axonal domains and the axon-glia interactions required for normal saltatory conduction.

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Available from: Hugo Bellen, Sep 28, 2015
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    • "The contactin-1–Caspr interaction is required for the transport and intracellular processing of contactin-1 (Gollan et al. 2003). Blocking the interaction between NF155 and the Caspr/contactin-1 complex inhibits myelination (Charles et al. 2002) and genetic ablation of genes encoding Caspr, contactin-1 or NF155 results both in the disruption of the paranodal septate-like junctions and in loss of ion channel segregation and impaired nerve conduction (Boyle et al. 2001; Bhat et al. 2001; Thaxton et al. 2010). In conclusion, interaction of glial NF155 with the axonal Caspr/contactin-1 complex is required for both nodal and paranodal stability. "
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    • "The biggest structural difference is that in the PNS, the nodes of Ranvier are apposed by nodal microvilli emanating from myelinating Schwann cells. These microvilli may play a role in local ion buffering, but also express gliomedin, a glial protein known to be important for the clustering of Nav channels at PNS nodes of Ranvier (for more information on PNS nodes of Ranvier see [13, 122]). Although CNS nodes of Ranvier are not contacted by protrusions of oligodendrocytes, they are often closely associated with astrocytic processes, the function of which remains unknown [58, 59]. "
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    • "We investigated the effect of IgGMOG + Chu on myelin and axonal proteins including myelin basic protein (MBP), neurofilament, ankyrin G (AnkG) and contactin associated protein (Caspr) (Figure  5B). MBP adheres adjacent cytoplasmic faces of myelin together, neurofilament provides structural support for axons, AnkG clusters voltage-gated Na+ channels at nodes of Ranvier [21] and Caspr attaches paranodal myelin loops to the axons [22]. At 24 hours after IgGMOG + Chu injection, MBP expression appeared abnormal (Figure  5C) and there was significant reduction in AnkG (Figure  5D) and Caspr (Figure  5E) immunoreactivities. "
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