Spatiotemporal ablation of myelinating glia-specificneurofascin(NfascNF155) in mice reveals gradual loss of paranodal axoglial junctions and concomitant disorganization of axonal domains
| Autor: | Alaine L. Pribisko, Manzoor A. Bhat, Anilkumar M. Pillai, Jr-Gang Cheng, Courtney Thaxton, Jeffrey L. Dupree |
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| Rok vydání: | 2009 |
| Předmět: |
Wallerian degeneration
Recombinant Fusion Proteins NFASC Neural Conduction Mice Transgenic Septate junctions Biology Nerve Fibers Myelinated Article Mice Cellular and Molecular Neuroscience Myelin Ranvier's Nodes medicine Animals Nerve Growth Factors Peripheral Nerves Myelin Proteolipid Protein Myelin Sheath Mice Knockout Movement Disorders Node of Ranvier medicine.disease Axons Mice Mutant Strains Axolemma Myelin proteolipid protein Disease Models Animal medicine.anatomical_structure nervous system Neuroglia Wallerian Degeneration Cell Adhesion Molecules Neuroscience Demyelinating Diseases |
| Zdroj: | Journal of Neuroscience Research. 87:1773-1793 |
| ISSN: | 1097-4547 0360-4012 |
| DOI: | 10.1002/jnr.22015 |
| Popis: | The evolutionary demand for rapid nerve impulse conduction led to the process of myelination-dependent organization of axons into distinct molecular domains. These domains include the node of Ranvier flanked by highly specialized paranodal domains where myelin loops and axolemma orchestrate the axoglial septate junctions. These junctions are formed by interactions between a glial isoform of neurofascin (Nfasc(NF155)) and axonal Caspr and Cont. Here we report the generation of myelinating glia-specific Nfasc(NF155) null mouse mutants. These mice exhibit severe ataxia, motor paresis, and death before the third postnatal week. In the absence of glial Nfasc(NF155), paranodal axoglial junctions fail to form, axonal domains fail to segregate, and myelinated axons undergo degeneration. Electrophysiological measurements of peripheral nerves from Nfasc(NF155) mutants revealed dramatic reductions in nerve conduction velocities. By using inducible PLP-CreER recombinase to ablate Nfasc(NF155) in adult myelinating glia, we demonstrate that paranodal axoglial junctions disorganize gradually as the levels of Nfasc(NF155) protein at the paranodes begin to drop. This coincides with the loss of the paranodal region and concomitant disorganization of the axonal domains. Our results provide the first direct evidence that the maintenance of axonal domains requires the fence function of the paranodal axoglial junctions. Together, our studies establish a central role for paranodal axoglial junctions in both the organization and the maintenance of axonal domains in myelinated axons. |
| Databáze: | OpenAIRE |
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