In VivoDeletion of Immunoglobulin Domains 5 and 6 inNeurofascin(Nfasc) Reveals Domain-Specific Requirements in Myelinated Axons
| Autor: | Courtney Thaxton, Anilkumar M. Pillai, Alaine L. Pribisko, Catherine Faivre-Sarrailh, Manzoor A. Bhat, Jeffrey L. Dupree, Marilyne Labasque |
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| Rok vydání: | 2010 |
| Předmět: |
Gene isoform
Transgene NFASC Immunoglobulins Mice Transgenic Septate junctions CHO Cells Immunoglobulin domain Biology Nerve Fibers Myelinated Article Mice Cricetulus Protein structure Cricetinae Protein Interaction Mapping Animals Humans Protein Isoforms Nerve Growth Factors Ion channel Mice Knockout Protein Stability General Neuroscience Molecular biology Axons Protein Structure Tertiary Rats Cell biology NODAL Cell Adhesion Molecules Gene Deletion |
| Zdroj: | The Journal of Neuroscience. 30:4868-4876 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5951-09.2010 |
| Popis: | The formation of paranodal axo-glial junctions is critical for the rapid and efficient propagation of nerve impulses. Genetic ablation of genes encoding the critical paranodal proteins Caspr, contactin (Cont), and the myelinating glia-specific isoform of Neurofascin (NfascNF155) results in the disruption of the paranodal axo-glial junctions, loss of ion channel segregation, and impaired nerve conduction, but the mechanisms regulating their interactions remain elusive. Here, we report that loss of immunoglobulin (Ig) domains 5 and 6 in NfascNF155in mice phenocopies complete ablation of NfascNF155. The mutant mice lack paranodal septate junctions, resulting in the diffusion of Caspr and Cont from the paranodes, and redistribution of the juxtaparanodal potassium channels toward the nodes. Although critical for NfascNF155function, we find that Ig5-6 are dispensable for nodal NfascNF186function. Moreover,in vitrobinding assays using Ig5-6 deletion constructs reveal their importance for the association of NfascNF155with Cont. These findings provide the first molecular evidence demonstrating domain-specific requirements controlling the association of the paranodal tripartite complexin vivo. Our studies further emphasize thatin vivostructure/function analysis is necessary to define the unique protein–protein interactions that differentially regulate the functions of Neurofascins during axonal domain organization. |
| Databáze: | OpenAIRE |
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