Molecular Constituents of the Node of Ranvier

Kazarinova-Noyes, Katie; Shrager, Peter

doi:10.1385/mn:26:2-3:167

Cited by 35 publications

(22 citation statements)

References 91 publications

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“…Normal node of Ranvier architecture and the clustering of Na ϩ channels within the node and K ϩ channels within the juxta-paranode depend on the presence of myelin (Kazarinova-Noyes and Shrager, 2002;Poliak and Peles, 2003). We examined Na ϩ and K ϩ channel density at the node and paranode in developing optic nerve of WAVE1Ϫ/Ϫ mice, finding reduced numbers of nodes compared with controls ( Fig.…”

Section: Wave1 Expression Increases At the Onset Of Myelination And Imentioning

confidence: 99%

WAVE1 Is Required for Oligodendrocyte Morphogenesis and Normal CNS Myelination

Kim¹,

DiBernardo²,

Rasband³

et al. 2006

J. Neurosci.

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Myelin formation involves the outgrowth of an oligodendrocyte cell process that can be regarded as a giant lamellipodium because it is an actively growing structure with extruded cytoplasm. The actin cytoskeleton is critical to morphogenesis, but little is known about regulation of actin dynamics in oligodendrocytes. Wiskott-Aldrich syndrome protein family verprolin homologous (WAVE) proteins mediate lamellipodia formation; thus, we asked whether these proteins function in oligodendrocyte process formation and myelination. Here, we show that WAVE1 is expressed by oligodendrocytes and localizes to the lamella leading edge where actin polymerization is actively regulated. CNS WAVE1 expression increases at the onset of myelination. Expression of dominant-negative WAVE1 impaired process outgrowth and lamellipodia formation in cultured oligodendrocytes. Similarly, oligodendrocytes isolated from mice lacking WAVE1 had fewer processes compared with controls, whereas neurons and astrocytes exhibited normal morphology. In white matter of WAVE1Ϫ/Ϫ mice, we found regional hypomyelination in the corpus callosum and to a lesser extent in the optic nerve. In optic nerve from WAVE1Ϫ/Ϫ mice, there were fewer nodes of Ranvier but nodal morphology was normal, implicating a defect in myelin formation. Our in vitro findings support a developmentally dynamic and cell-autonomous role for WAVE1 in regulating process formation in oligodendrocytes. Additionally, WAVE1 function during CNS myelination appears to be linked to regional cues. Although its loss can be compensated for in many CNS regions, WAVE1 is clearly required for normal amounts of myelin to form in corpus callosum and optic nerve. Together, these data demonstrate a role for WAVE1 in oligodendrocyte morphogenesis and myelination.

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Section: Wave1 Expression Increases At the Onset Of Myelination And Imentioning

confidence: 99%

WAVE1 Is Required for Oligodendrocyte Morphogenesis and Normal CNS Myelination

Kim¹,

DiBernardo²,

Rasband³

et al. 2006

J. Neurosci.

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“…Contactin deficiency could thus limit the number of sodium channels on axon surfaces, and thereby decrease neuronal activity, which is crucial for myelination and oligodendrocyte differentiation in vitro and in vivo (56)(57)(58)(59). Indeed, Kazarinova-Noyes and Shrager recorded reduced compound action potential velocity in Cntn1-KO optic nerves (60). In Cntn1-KO nerves, diminished nerve activity could impact signals for initiating myelination by resident oligodendrocytes, and reduce subsequent paranode-and node formation.…”

Section: Contactin In Domain Organization Of Myelinated Central Nervesmentioning

confidence: 99%

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

Çolakoğlu

Bergstrom-Tyrberg

Berglund

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the CNS, enables rapid nerve impulse conduction and sustains neuronal health. The signals exchanged between axons and oligodendrocytes in myelin remain to be fully elucidated. Here we provide genetic evidence for multiple and critical functions of Contactin-1 in central myelin. We document dynamic Contactin-1 expression on oligodendrocytes in vivo, and progressive accumulation at nodes of Ranvier and paranodes during postnatal mouse development. Nodal and paranodal expression stabilized in mature myelin, but overall membranous expression diminished. Contactin-1-deficiency disrupted paranodal junction formation as evidenced by loss of Caspr, mislocalized potassium K v 1.2 channels, and abnormal myelin terminal loops. Reduced numbers and impaired maturation of sodium channel clusters accompanied this phenotype. Histological, electron microscopic, and biochemical analyses uncovered significant hypomyelination in Contactin-1-deficient central nerves, with up to 60% myelin loss. Oligodendrocytes were present in normal numbers, albeit a minor population of neuronal/glial antigen 2-positive (NG2 + ) progenitors lagged in maturation by postnatal day 18, when the mouse null mutation was lethal. Major contributing factors to hypomyelination were defects in the generation and organization of myelin membranes, as judged by electron microscopy and quantitative analysis of oligodendrocyte processes labeled by GFP transgenically expressed from the proteolipid protein promoter. These data reveal that Contactin-1 regulates both myelin formation and organization of nodal and paranodal domains in the CNS. These multiple roles distinguish central Contactin-1 functions from its specific role at paranodes in the periphery, and emphasize mechanistic differences in central and peripheral myelination.

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“…The maturation of a node of Ranvier is essential for the saltatory conduction of action potentials along myelinated axons. Due to their crucial role in signal transduction, the molecular mechanisms underlying the formation of nodes of Ranvier have been extensively studied, [47][48][49][50] and some hypotheses and models have been suggested and discussed. [51][52][53] However, the inability to observe nodes of Ranvier in real time has greatly limited our knowledge on the mechanisms of their dynamic formation.…”

Section: In Vivo Imaging To Monitor the Development Of A Single Node mentioning

confidence: 99%

Label-free real-time imaging of myelination in theXenopus laevistadpole byin vivostimulated Raman scattering microscopy

Zhang

Slipchenko

et al. 2014

J. Biomed. Opt

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Abstract. The myelin sheath plays an important role as the axon in the functioning of the neural system, and myelin degradation is a hallmark pathology of multiple sclerosis and spinal cord injury. Electron microscopy, fluorescent microscopy, and magnetic resonance imaging are three major techniques used for myelin visualization. However, microscopic observation of myelin in living organisms remains a challenge. Using a newly developed stimulated Raman scattering microscopy approach, we report noninvasive, label-free, real-time in vivo imaging of myelination by a single-Schwann cell, maturation of a single node of Ranvier, and myelin degradation in the transparent body of the Xenopus laevis tadpole.

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Molecular Constituents of the Node of Ranvier

Cited by 35 publications

References 91 publications

WAVE1 Is Required for Oligodendrocyte Morphogenesis and Normal CNS Myelination

WAVE1 Is Required for Oligodendrocyte Morphogenesis and Normal CNS Myelination

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

Label-free real-time imaging of myelination in theXenopus laevistadpole byin vivostimulated Raman scattering microscopy

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