Spectrins and AnkyrinB Constitute a Specialized Paranodal Cytoskeleton

Ogawa, Yasuhiro; Schafer, Dorothy P.; Horresh, Ido; Bar, Vered; Hales, Kimberly; Yang, Yang; Susuki, Keiichiro; Peles, Elior; Stankewich, Michael C.; Rasband, Matthew N.

doi:10.1523/jneurosci.0425-06.2006

Cited by 149 publications

(180 citation statements)

References 53 publications

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“…Other avenues, such as non-specific leakages due to membrane damage, may be dominant factors in this case (Shi and Whitebone, 2006;. The paranodal septate junction is an axonal-glial protein complex that is comprised of contactin-associated protein (Caspr), Nfac 155, contactin, spectrin, protein 4.1, and actin (Bhat, 2003;Bhat et al, 2001;Girault and Peles, 2002;Gollan et al, 2003;Ogawa et al, 2006;Susuki and Rasband, 2008). Both protein 4.1 and spectrin are known calpain substrates (Goll et al, 2003), and calpain itself is a calcium-dependent protease.…”

Section: Discussionmentioning

confidence: 99%

Paranodal Myelin Damage after Acute Stretch in Guinea Pig Spinal Cord

Sun

Shi

et al. 2012

Journal of Neurotrauma

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Mechanical injury causes myelin disruption and subsequent axonal conduction failure in the mammalian spinal cord. However, the underlying mechanism is not well understood. In mammalian myelinated axons, proper paranodal myelin structure is crucial for the generation and propagation of action potentials. The exposure of potassium channels at the juxtaparanodal region due to myelin disruption is thought to induce outward potassium currents and inhibit the genesis of the action potential, leading to conduction failure. Using multimodal imaging techniques, we provided anatomical evidence demonstrating paranodal myelin disruption and consequent exposure and redistribution of potassium channels following mechanical insult in the guinea pig spinal cord. Decompaction of paranodal myelin was also observed. It was shown that paranodal demyelination can result from both an initial physical impact and secondary biochemical reactions that are calcium dependent. 4-Aminopyridine (4-AP), a known potassium channel blocker, can partially restore axonal conduction, which further implicates the role of potassium channels in conduction failure. We provide important evidence of paranodal myelin damage, the role of potassium channels in conduction loss, and the therapeutic value of potassium blockade as an effective intervention to restore function following spinal cord trauma.

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Section: Discussionmentioning

confidence: 99%

Paranodal Myelin Damage after Acute Stretch in Guinea Pig Spinal Cord

Sun

Shi

et al. 2012

Journal of Neurotrauma

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“…This strong binding of NF and ankG might reflect a stabilizing role for NF and ankG in building the IS as a stable specialized membrane domain. ankG and ankB are also spatially segregated in myelinated axons and might contribute to organizing nodal and paranodal domains as well (Ogawa et al, 2006). L1, conversely, shows spatial and temporal regulation of its ankyrin binding.…”

Section: Ankyrin Binding In L1 Family Member Biologymentioning

confidence: 99%

Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron–Glia Cell Adhesion Molecule

Boiko¹,

Vakulenko²,

Ewers³

et al. 2007

J. Neurosci.

114

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Axonal initial segments (IS) and nodes of Ranvier are functionally important membrane subdomains in which the clustering of electrogenic channels enables action potential initiation and propagation. In addition, the initial segment contributes to neuronal polarity by serving as a diffusion barrier. To study the mechanisms of axonal compartmentalization, we focused on two L1 family of cell adhesion molecules (L1-CAMs) [L1/neuron-glia cell adhesion molecule (L1/NgCAM) and neurofascin (NF)] and two neuronal ankyrins (ankB and ankG). NF and ankG accumulate specifically at the initial segment, whereas L1/NgCAM and ankB are expressed along the entire lengths of axons. We find that L1/NgCAM and NF show distinct modes of steady-state accumulation during axon outgrowth in cultured hippocampal neurons. Despite their different steady-state localizations, both L1/NgCAM and NF show slow diffusion and low detergent extractability specifically in the initial segment but fast diffusion and high detergent extractability in the distal axon. We propose that L1-CAMs do not strongly bind ankB in the distal axon because of spatial regulation of ankyrin affinity by phosphorylation. NF, conversely, is initially enriched in an ankyrin-independent manner in the axon generally and accumulates progressively in the initial segment attributable to preferential binding to ankG. Our results suggest that NF and L1/NgCAM accumulate in the axon by an ankyrinindependent pathway, but retention at the IS requires ankyrin binding.

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“…It should be noted that Na + /K + -ATPase is a component of septate junctions in Drosophila and is required for their function (Genova and Fehon, 2003;Paul et al, 2003) and that Na + / K + -ATPase subunits have recently been detected by mass spectroscopy in paranodal membrane preparations (Ogawa et al, 2006). However, it is not yet known whether Na + /K + -ATPase plays a role in the function of paranodal junctions.…”

Section: Potential Mechanisms Of Nmv Formationmentioning

confidence: 99%

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

2006

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Mitochondria and other membranous organelles are frequently enriched in the nodes and paranodes of peripheral myelinated axons, particularly those of large caliber. The physiologic role(s) of this organelle enrichment and the rheologic factors that regulate it are not well understood. Previous studies suggest that axonal transport of organelles across the nodal/paranodal region is locally regulated. In this study, we have examined the ultrastructure of myelinated axons in the sciatic nerves of mice deficient in the contactin-associated protein (Caspr), an integral junctional component. These mice, which lack the normal septate-like junctions that promote attachment of the glial (paranodal) loops to the axon, contain aberrant mitochondria in their nodal/ paranodal regions. These mitochondria are typically large and swollen and occupy prominent varicosities of the nodal axolemma. In contrast, mitochondria located outside the nodal/paranodal regions of the myelinated axons appear normal. These findings suggest that paranodal junctions regulate mitochondrial transport and function in the axoplasm of the nodal/paranodal region of myelinated axons of peripheral nerves. They further implicate the paranodal junctions in playing a role, either directly or indirectly, in the local regulation of energy metabolism in the nodal region.

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Spectrins and AnkyrinB Constitute a Specialized Paranodal Cytoskeleton

Cited by 149 publications

References 53 publications

Paranodal Myelin Damage after Acute Stretch in Guinea Pig Spinal Cord

Paranodal Myelin Damage after Acute Stretch in Guinea Pig Spinal Cord

Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron–Glia Cell Adhesion Molecule

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

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