βIV Spectrins Are Essential for Membrane Stability and the Molecular Organization of Nodes of Ranvier
Open Access
- 18 August 2004
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 24 (33), 7230-7240
- https://doi.org/10.1523/jneurosci.2125-04.2004
Abstract
High densities of sodium channels at nodes of Ranvier permit action potential conduction and depend on βIV spectrins, a family of scaffolding proteins linked to the cortical actin cytoskeleton. To investigate the molecular organization of nodes, we analyzedqv3J“quivering” mice, whose βIV spectrins have a truncated proline-rich “specific” domain (SD) and lack the pleckstrin homology (PH) domain. Central nodes ofqv3Jmice, which lack βIV spectrins, are significantly broader and have prominent vesicle-filled nodal membrane protrusions, whereas axon shape and neurofilament density are dramatically altered. PNSqv3Jnodes, some with detectable βIV spectrins, are less affected. In contrast, a larger truncation of βIV spectrins inqv4Jmice, deleting the SD, PH, and ankyrinG binding domains, causes βIV spectrins to be undetectable and causes dramatic changes, even in peripheral nodes. These results show that quivering mutations disrupt βIV spectrin retention and stability at nodes and that distinct protein domains regulate nodal structural integrity and molecular organization.Keywords
This publication has 49 references indexed in Scilit:
- Does Paranode Formation and Maintenance Require Partitioning of Neurofascin 155 into Lipid Rafts?Journal of Neuroscience, 2004
- Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient formation of nodes of RanvierThe Journal of cell biology, 2003
- Paranodal transverse bands are required for maintenance but not initiation of Nav1.6 sodium channel clustering in CNS optic nerve axonsGlia, 2003
- Dysregulation of axonal sodium channel isoforms after adult‐onset chronic demyelinationJournal of Neuroscience Research, 2003
- βIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of RanvierThe Journal of cell biology, 2002
- Ezrin, radixin, and moesin are components of Schwann cell microvilliJournal of Neuroscience Research, 2001
- A New Spectrin, βIV, Has a Major Truncated Isoform That Associates with Promyelocytic Leukemia Protein Nuclear Bodies and the Nuclear MatrixPublished by Elsevier BV ,2001
- Generation and Characterization of Subtype-specific Monoclonal Antibodies to K+ Channel α- and β-subunit PolypeptidesNeuropharmacology, 1996
- Co-localization of the myelin-associated glycoprotein and the microfilament components, F-actin and spectrin, in Schwann cells of myelinated nerve fibresJournal of Neurocytology, 1989
- Selective Solubilization of a Protein Component of the Red Cell MembraneScience, 1968