Résumé :
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Communication n° 496. Myelination allows the fast propagation of action potentials at a low energetic cost. It provides an insulating myelin sheath, regularly interrupted at the nodes of Ranvier where are concentrated voltage-gated Na+ channels which allow the generation of action potential. The nodes of Ranvier represent an essential functional region of the myelinated fibers where myelinating glial cells exchange highly differentiated and exquisitely organized contacts with the axon. These interactions determine the formation of distinct anatomical and functional domains on the axon called the node, the paranode and the juxtaparanode. We, and others, have identified some of the major molecular complexes that underlie these interactions at the level of paranodes and juxtaparanodes. These complexes are based on evolutionary conserved multimolecular complexes comprising an axonal transmembrane protein of the Neurexin-IV-Caspr-Paranodin family (NCP) associated with a protein of the contactin family, a group of glycosylphosphatidyl-anchored immunoglobulin superfamily cell adhesion molecules (IgSF-CAM). These two proteins interact with a glial IgSF-CAM forming core ternary complexes. These complexes are essential for structural and functional axoglial interactions. By electron microscopy the axoplasm at the nodes of Ranvier seems tightly attached to the axonal cytoskeleton. We have identified a protein, 4.1B, which is able to associate with the cytoplasmic regions of the NCP proteins and that may provide links between the paranodal and juxtaparanodal axoglial complexes and the axonal cytoskeleton. In order to determine the significance of this observation, we have started the analysis of knockout mice for 4.1B. Our preliminary results show that 4.1B seems to play a critical role in the organization of the nodes of Ranvier and of the myelinated fibers in general.
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