The making of a node: a co-production of neurons and glia

Eshed-Eisenbach, Yael; Peles, Elior

doi:10.1016/j.conb.2013.06.003

Cited by 39 publications

(29 citation statements)

References 83 publications

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“…However, nodes of Ranvier require participation of glial cells and neurons where glial NF155 assembles the axoglial junction, and the neuronal NF186 isoform clusters AnkG at the node, followed by subsequent secondary recruitment of VGSCs (reviewed in ref. 30). In addition, other mechanisms participate in node assembly, including glial-derived extracellular matrix-mediated clustering of NF186, restriction of nodal protein mobility through a paranodal barrier, and stabilization of nodal proteins through interactions with the cytoskeleton (52,53).…”

Section: Resultsmentioning

confidence: 99%

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Giant ankyrin-G: A critical innovation in vertebrate evolution of fast and integrated neuronal signaling

Jenkins

Kim²,

Jones

et al. 2014

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

149

222

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Axon initial segments (AISs) and nodes of Ranvier are sites of clustering of voltage-gated sodium channels (VGSCs) in nervous systems of jawed vertebrates that facilitate fast long-distance electrical signaling. We demonstrate that proximal axonal polarity as well as assembly of the AIS and normal morphogenesis of nodes of Ranvier all require a heretofore uncharacterized alternatively spliced giant exon of ankyrin-G (AnkG). This exon has sequence similarity to I-connectin/Titin and was acquired after the first round of whole-genome duplication by the ancestral ANK2/ANK3 gene in early vertebrates before development of myelin. The giant exon resulted in a new nervous system-specific 480-kDa polypeptide combining previously known features of ANK repeats and β-spectrin-binding activity with a fibrous domain nearly 150 nm in length. We elucidate previously undescribed functions for giant AnkG, including recruitment of β4 spectrin to the AIS that likely is regulated by phosphorylation, and demonstrate that 480-kDa AnkG is a major component of the AIS membrane "undercoat' imaged by platinum replica electron microscopy. Surprisingly, giant AnkG-knockout neurons completely lacking known AIS components still retain distal axonal polarity and generate action potentials (APs), although with abnormal frequency. Giant AnkG-deficient mice live to weaning and provide a rationale for survival of humans with severe cognitive dysfunction bearing a truncating mutation in the giant exon. The giant exon of AnkG is required for assembly of the AIS and nodes of Ranvier and was a transformative innovation in evolution of the vertebrate nervous system that now is a potential target in neurodevelopmental disorders.neuropsychiatric disease | cognitive impairment disorder | axon initial segment | ankyrin-G | axonal polarity

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Section: Resultsmentioning

confidence: 99%

“…Nodes of Ranvier, which evolved later than the AIS (29), share a similar AnkG-based interactome but require axonal-glial interactions as well as extracellular matrix for their formation (reviewed in ref. 30).…”

mentioning

confidence: 99%

Giant ankyrin-G: A critical innovation in vertebrate evolution of fast and integrated neuronal signaling

Jenkins

Kim²,

Jones

et al. 2014

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

149

222

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“…Although myelination of axons does not alter the patterning of the subcortical cytoskeleton (5,6), it changes its molecular composition, promoting the clustering of specific markers at the nodes of Ranvier, where the action potential is regenerated (reviewed in refs. 7,8). At nodes of Ranvier, the myelin sheath formed by oligodendrocytes (in the CNS) or Schwann cells (in the PNS) is interrupted.…”

mentioning

confidence: 99%

Ultrastructural anatomy of nodes of Ranvier in the peripheral nervous system as revealed by STED microscopy

D’Este

Kamin

Balzarotti

et al. 2016

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

116

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We used stimulated emission depletion (STED) superresolution microscopy to analyze the nanoscale organization of 12 glial and axonal proteins at the nodes of Ranvier of teased sciatic nerve fibers. Cytoskeletal proteins of the axon (betaIV spectrin, ankyrin G) exhibit a high degree of one-dimensional longitudinal order at nodal gaps. In contrast, axonal and glial nodal adhesion molecules [neurofascin-186, neuron glial-related cell adhesion molecule (NrCAM)] can arrange in a more complex, 2D hexagonal-like lattice but still feature a ∼190-nm periodicity. Such a lattice-like organization is also found for glial actin. Sodium and potassium channels exhibit a one-dimensional periodicity, with the Na v channels appearing to have a lower degree of organization. At paranodes, both axonal proteins (betaII spectrin, Caspr) and glial proteins (neurofascin-155, ankyrin B) form periodic quasi-one-dimensional arrangements, with a high degree of interdependence between the position of the axonal and the glial proteins. The results indicate the presence of mechanisms that finely align the cytoskeleton of the axon with the one of the Schwann cells, both at paranodal junctions (with myelin loops) and at nodal gaps (with microvilli). Taken together, our observations reveal the importance of the lateral organization of proteins at the nodes of Ranvier and pave the way for deeper investigations of the molecular ultrastructural mechanisms involved in action potential propagation, the formation of the nodes, axon-glia interactions, and demyelination diseases.nodes of Ranvier | STED nanoscopy | cytoskeleton | axon-glia interaction | sciatic nerve I n recent years, knowledge of the ultrastructural organization of the axon initial segment (AIS) has been greatly extended by using optical nanoscopy to visualize its molecular composition. Stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion (STED) microscopy were indeed crucial for the identification of a ∼190-nm periodic organization of the key components of the AIS. In particular, a periodic spatial arrangement was discovered for cytoskeletal proteins (actin, ankyrin G, betaIV spectrin), adhesion molecules (neurofascin), and channels (voltage-gated sodium Na v channels) (1-4). In the distal part of the axon, this periodicity has been found for actin, adducin, ankyrin B, and betaII spectrin in virtually every neuron type from the central and peripheral nervous systems (CNS and PNS) (1, 2, 5, 6). Although myelination of axons does not alter the patterning of the subcortical cytoskeleton (5, 6), it changes its molecular composition, promoting the clustering of specific markers at the nodes of Ranvier, where the action potential is regenerated (reviewed in refs. 7, 8). At nodes of Ranvier, the myelin sheath formed by oligodendrocytes (in the CNS) or Schwann cells (in the PNS) is interrupted. Still, the nodal gap is surrounded by perinodal astrocytes and microvilli stemming from the Schwann cells in the CNS and PNS, respectively (9). Interestingly, the AIS an...

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“…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. By using a SRS microscope, we were able to observe the developmental behavior of a node of Ranvier in a stage 49 tadpole in real time.…”

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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The making of a node: a co-production of neurons and glia

Cited by 39 publications

References 83 publications

Giant ankyrin-G: A critical innovation in vertebrate evolution of fast and integrated neuronal signaling

Giant ankyrin-G: A critical innovation in vertebrate evolution of fast and integrated neuronal signaling

Ultrastructural anatomy of nodes of Ranvier in the peripheral nervous system as revealed by STED microscopy

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

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