Three Mechanisms Assemble Central Nervous System Nodes of Ranvier
| Autor: | Yasuhiro Ogawa, Constanze I. Seidenbecher, Dieter R. Zimmermann, Toshitaka Oohashi, Yael Eshed-Eisenbach, Keiichiro Susuki, Elior Peles, Kae-Jiun Chang, Alma L. Burlingame, Matthew N. Rasband, María T. Dours-Zimmermann, Juan A. Oses-Prieto, Yanhong Liu, Daniel R. Zollinger |
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| Přispěvatelé: | University of Zurich, Rasband, Matthew N |
| Jazyk: | angličtina |
| Předmět: |
Central Nervous System
Motor dysfunction Multiple Sclerosis Action potential Knockout Neuroscience(all) Central nervous system Action Potentials 610 Medicine & health Biology Neurodegenerative Autoimmune Disease Sodium Channels Article Extracellular matrix Mice 10049 Institute of Pathology and Molecular Pathology Ranvier's Nodes medicine Psychology Animals Cytoskeleton Myelin Sheath Mice Knockout Neurology & Neurosurgery Cell adhesion molecule General Neuroscience Neurosciences 2800 General Neuroscience Axons Cell biology Brain Disorders Extracellular Matrix medicine.anatomical_structure nervous system Neurological Cognitive Sciences Proteoglycans NODAL Neuroscience Cell Adhesion Molecules |
| Zdroj: | Neuron, vol 78, iss 3 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2013.03.005 |
| Popis: | SummaryRapid action potential propagation in myelinated axons requires Na+ channel clustering at nodes of Ranvier. However, the mechanism of clustering at CNS nodes remains poorly understood. Here, we show that the assembly of nodes of Ranvier in the CNS involves three mechanisms: a glia-derived extracellular matrix (ECM) complex containing proteoglycans and adhesion molecules that cluster NF186, paranodal axoglial junctions that function as barriers to restrict the position of nodal proteins, and axonal cytoskeletal scaffolds (CSs) that stabilize nodal Na+ channels. We show that while mice with a single disrupted mechanism had mostly normal nodes, disruptions of the ECM and paranodal barrier, the ECM and CS, or the paranodal barrier and CS all lead to juvenile lethality, profound motor dysfunction, and significantly reduced Na+ channel clustering. Our results demonstrate that ECM, paranodal, and axonal cytoskeletal mechanisms ensure robust CNS nodal Na+ channel clustering. |
| Databáze: | OpenAIRE |
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