scholarly journals Clusters of neuronal Neurofascin prefigure node of Ranvier position along single axons

2021 ◽  
Author(s):  
Stavros Vagionitis ◽  
Franziska Auer ◽  
Yan Xiao ◽  
Rafael G Almeida ◽  
David Lyons ◽  
...  
Keyword(s):  
Cell Adhesion Molecule ◽  
Node Of Ranvier ◽  
Nodes Of Ranvier ◽  
Additional Mechanism ◽  
Myelin Sheaths ◽  
Stable Clusters ◽  
Change Position ◽  
Node Position ◽  
Node Formation ◽  
Conduction Properties

The spacing of nodes of Ranvier crucially affects conduction properties along myelinated axons. It has been assumed that node position is primarily driven by the growth of myelin sheaths. Here, we reveal an additional mechanism of node positioning that is driven by the axon. We show through longitudinal live imaging of node formation dynamics that stable clusters of the cell adhesion molecule Neurofascin A accumulate at specific sites along axons prior to myelination. While some of these clusters change position upon encounter with growing myelin sheaths, others restrict sheath extension and are therefore predictive of future node position. Animals that lack full-length Neurofascin A showed increased internodal distances and less regular spacing of nodes along single axons. Together, our data reveal the existence of an axonal mechanism to position its nodes of Ranvier that does not depend on regulation of myelin sheath length.

scholarly journals Early events in node of Ranvier formation during myelination and remyelination in the PNS

2006 ◽  
Vol 2 (2) ◽  
pp. 69-79 ◽  
Author(s):  
DOROTHY P. SCHAFER ◽  
ANDREW W. CUSTER ◽  
PETER SHRAGER ◽  
MATTHEW N. RASBAND
Keyword(s):  
Cell Adhesion ◽  
Action Potential ◽  
Adhesion Molecule ◽  
Myelin Sheath ◽  
Cell Adhesion Molecule ◽  
Node Of Ranvier ◽  
Voltage Gated ◽  
Nav Channels ◽  
Node Formation ◽  
Peripheral Node

Action potential conduction velocity increases dramatically during early development as axons become myelinated. Integral to this process is the clustering of voltage-gated Na+ (Nav) channels at regularly spaced gaps in the myelin sheath called nodes of Ranvier. We show here that some aspects of peripheral node of Ranvier formation are distinct from node formation in the CNS. For example, at CNS nodes, Nav1.2 channels are detected first, but are then replaced by Nav1.6. Similarly, during remyelination in the CNS, Nav1.2 channels are detected at newly forming nodes. By contrast, the earliest Nav-channel clusters detected during developmental myelination in the PNS have Nav1.6. Further, during PNS remyelination, Nav1.6 is detected at new nodes. Finally, we show that accumulation of the cell adhesion molecule neurofascin always precedes Nav channel clustering in the PNS. In most cases axonal neurofascin (NF-186) accumulates first, but occasionally paranodal neurofascin is detected first. We suggest there is heterogeneity in the events leading to Nav channel clustering, indicating that multiple mechanisms might contribute to node of Ranvier formation in the PNS.

Early Reactive Changes at Myelin Sheaths Gaps (nodes of Ranvier) of Nerve Fibers (a supravital study)

2012 ◽  
Vol 42 (7) ◽  
pp. 775-779
Author(s):  
O. S. Sotnikov ◽  
T. N. Kokurina ◽  
I. A. Solovyova ◽  
S. S. Sergeeva
Keyword(s):  
Nerve Fibers ◽  
Nodes Of Ranvier ◽  
Myelin Sheaths ◽  
Reactive Changes

scholarly journals An Oligodendrocyte Cell Adhesion Molecule at the Site of Assembly of the Paranodal Axo-Glial Junction

2000 ◽  
Vol 150 (3) ◽  
pp. 657-666 ◽  
Author(s):  
Steven Tait ◽  
Frank Gunn-Moore ◽  
J. Martin Collinson ◽  
Jeffery Huang ◽  
Catherine Lubetzki ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Peripheral Nerves ◽  
Cell Adhesion Molecule ◽  
Close Association ◽  
Node Of Ranvier ◽  
Septate Junction ◽  
Adhesion Zone ◽  
Paranodal Junctions ◽  
The Central Nervous System

Two major isoforms of the cell adhesion molecule neurofascin NF186 and NF155 are expressed in the central nervous system (CNS). We have investigated their roles in the assembly of the node of Ranvier and show that they are targeted to distinct domains at the node. At the onset of myelination, NF186 is restricted to neurons, whereas NF155 localizes to oligodendrocytes, the myelin-forming glia of the CNS. Coincident with axon ensheathment, NF155 clusters at the paranodal regions of the myelin sheath where it localizes in apposition to the axonal adhesion molecule paranodin/contactin-associated protein (Caspr1), which is a constituent of the septate junction-like axo-glial adhesion zone. Immunoelectron microscopy confirmed that neurofascin is a glial component of the paranodal axo-glial junction. Concentration of NF155 with Caspr1 at the paranodal junctions of peripheral nerves is also a feature of Schwann cells. In Shiverer mutant mice, which assemble neither compact CNS myelin nor normal paranodes, NF155 (though largely retained at the cell body) is also distributed at ectopic sites along axons, where it colocalizes with Caspr1. Hence, NF155 is the first glial cell adhesion molecule to be identified in the paranodal axo-glial junction, where it likely interacts with axonal proteins in close association with Caspr1.

scholarly journals Sodium channel β1 and β3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain

2001 ◽  
Vol 154 (2) ◽  
pp. 427-434 ◽  
Author(s):  
Charlotte F. Ratcliffe ◽  
Ruth E. Westenbroek ◽  
Rory Curtis ◽  
William A. Catterall
Keyword(s):  
Cell Adhesion ◽  
Sodium Channel ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neuronal Cell ◽  
Nodes Of Ranvier ◽  
Neuronal Cell Adhesion Molecule ◽  
Fibronectin Type Iii ◽  
A Cell ◽  
Fibronectin Type

Sequence homology predicts that the extracellular domain of the sodium channel β1 subunit forms an immunoglobulin (Ig) fold and functions as a cell adhesion molecule. We show here that β1 subunits associate with neurofascin, a neuronal cell adhesion molecule that plays a key role in the assembly of nodes of Ranvier. The first Ig-like domain and second fibronectin type III–like domain of neurofascin mediate the interaction with the extracellular Ig-like domain of β1, confirming the proposed function of this domain as a cell adhesion molecule. β1 subunits localize to nodes of Ranvier with neurofascin in sciatic nerve axons, and β1 and neurofascin are associated as early as postnatal day 5, during the period that nodes of Ranvier are forming. This association of β1 subunit extracellular domains with neurofascin in developing axons may facilitate recruitment and concentration of sodium channel complexes at nodes of Ranvier.

scholarly journals Motor Learning Drives Dynamic Patterns of Intermittent Myelination on Behaviorally-Activated Axons

2021 ◽  
Author(s):  
Clara M. Bacmeister ◽  
Rongchen Huang ◽  
Michael A. Thornton ◽  
Lauren Conant ◽  
Anthony R. Chavez ◽  
...  
Keyword(s):  
Motor Learning ◽  
Computational Modeling ◽  
Learning And Memory ◽  
Neuronal Activity ◽  
Neural Circuits ◽  
Cortical Layers ◽  
Nodes Of Ranvier ◽  
Two Photon ◽  
Myelin Sheaths

Myelin plasticity occurs when newly-formed and pre-existing oligodendrocytes remodel existing myelination. Recent studies show these processes occur in response to changes in neuronal activity and are required for learning and memory. However, the link between behaviorally-relevant neuronal activity and circuit-specific changes in myelination remains unknown. Using longitudinal, in vivo two-photon imaging and targeted labeling of behaviorally-activated neurons, we explore how the pattern of intermittent myelination is altered on individual cortical axons during learning of a dexterous reach task. We show that learning-induced plasticity is targeted to behaviorally-activated axons and occurs in a staged response across cortical layers. During learning, myelin sheaths retract, lengthening nodes of Ranvier. Following learning, addition of new sheaths increases the number of continuous stretches of myelination. Computational modeling suggests these changes initially slow and subsequently increase conduction speed. Thus, behaviorally-activated, circuit-specific changes to myelination may fundamentally alter how information is transferred in neural circuits during learning.

scholarly journals Neuronal cell adhesion molecules and cytotactin are colocalized at the node of Ranvier.

1986 ◽  
Vol 103 (2) ◽  
pp. 379-391 ◽  
Author(s):  
F Rieger ◽  
J K Daniloff ◽  
M Pincon-Raymond ◽  
K L Crossin ◽  
M Grumet ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Schwann Cells ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Matrix Protein ◽  
Neuronal Cell ◽  
Extracellular Matrix Protein ◽  
Nodes Of Ranvier ◽  
Intense Staining ◽  
Adult Chicken

Immunocytochemical methods were used to show that Ng-CAM (the neuron-glia cell adhesion molecule), N-CAM (the neural cell adhesion molecule), and the extracellular matrix protein cytotactin are highly concentrated at nodes of Ranvier of the adult chicken and mouse. In contrast, unmyelinated axonal fibers were uniformly stained by specific antibodies to both CAMs but not by antibodies to cytotactin. Ultrastructural immunogold techniques indicated that both N-CAM and Ng-CAM were enriched in the nodal axoplasm and axolemma of myelinated fibers as well as within the nodal regions of the myelinating Schwann cell. At embryonic day 14, before myelination had occurred, small-caliber fibers of chick embryos showed periodic coincident accumulations of the two CAMs but not of cytotactin, with faint labeling in the axonal regions between accumulations. Cytotactin was found on Schwann cells and in connective tissue. By embryonic day 18, nodal accumulations of CAMs were first observed in a few medium- and large-caliber fibers. Immunoblot analyses indicated that embryonic to adult conversion of N-CAM and a progressive decrease in the amount of Ng-CAM and N-CAM occurred while nodes were forming. Sciatic nerves of mouse mutants with defects in cell interactions showed abnormalities in the distribution patterns and amount of Ng-CAM, N-CAM, and cytotactin that were consistent with the known morphological nodal disorders. In trembler (+/Tr), intense staining for both CAMs appeared all along the fibers and the amounts of N-CAM in the sciatic nerve were found to be increased. In mice with motor endplate disease (med/med), Ng-CAM and N-CAM, but not cytotactin, were localized in the widened nodes. Both trembler and med/med Schwann cells stained intensely for cytotactin, in contrast to normal Schwann cells which stained only slightly. All of these findings are consistent with the hypothesis that surface modulation of neuronal CAMs mediated by signals shared between neurons and glia may be necessary for establishing and maintaining the nodes of Ranvier.

scholarly journals Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
R. Ronzano ◽  
T. Roux ◽  
M. Thetiot ◽  
M. S. Aigrot ◽  
L. Richard ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Neurological Diseases ◽  
Node Of Ranvier ◽  
Dynamic Imaging ◽  
Nodes Of Ranvier ◽  
Potassium Release ◽  
Neuron Interaction ◽  
The Central Nervous System ◽  
Myelin Injury ◽  
Brain Homeostasis

AbstractMicroglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct site of interaction between microglia and axons, in both mouse and human tissues. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglia-node interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Altered axonal K+ flux following demyelination impairs the switch towards a pro-regenerative microglia phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron interaction, that may participate in microglia-neuron communication mediating pro-remyelinating effect of microglia after myelin injury.

scholarly journals Perlecan is recruited by dystroglycan to nodes of Ranvier and binds the clustering molecule gliomedin

2015 ◽  
Vol 208 (3) ◽  
pp. 313-329 ◽  
Author(s):  
Cristina Colombelli ◽  
Marilena Palmisano ◽  
Yael Eshed-Eisenbach ◽  
Desirée Zambroni ◽  
Ernesto Pavoni ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Basal Lamina ◽  
Node Of Ranvier ◽  
Na Channel ◽  
Na Channels ◽  
Nodes Of Ranvier ◽  
Neural Conduction ◽  
Matrix Components ◽  
Selective Accumulation

Fast neural conduction requires accumulation of Na+ channels at nodes of Ranvier. Dedicated adhesion molecules on myelinating cells and axons govern node organization. Among those, specific laminins and dystroglycan complexes contribute to Na+ channel clustering at peripheral nodes by unknown mechanisms. We show that in addition to facing the basal lamina, dystroglycan is found near the nodal matrix around axons, binds matrix components, and participates in initial events of nodogenesis. We identify the dystroglycan-ligand perlecan as a novel nodal component and show that dystroglycan is required for the selective accumulation of perlecan at nodes. Perlecan binds the clustering molecule gliomedin and enhances clustering of node of Ranvier components. These data show that proteoglycans have specific roles in peripheral nodes and indicate that peripheral and central axons use similar strategies but different molecules to form nodes of Ranvier. Further, our data indicate that dystroglycan binds free matrix that is not organized in a basal lamina.

scholarly journals Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments.

1996 ◽  
Vol 135 (5) ◽  
pp. 1355-1367 ◽  
Author(s):  
J Q Davis ◽  
S Lambert ◽  
V Bennett
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Node Of Ranvier ◽  
Full Length ◽  
Nodes Of Ranvier ◽  
The Third ◽  
Fniii Domain ◽  
Axon Initial Segments ◽  
Binding Cell

Neurofascin, NrCAM, L1, and NgCAM are a family of Ig/FNIII cell adhesion molecules that share ankyrin-binding activity in their cytoplasmic domains, and are candidates to form membrane-spanning complexes with members of the ankyrin family of spectrin-binding proteins in a variety of cellular contexts in the nervous system. Specialized forms of ankyrin, 270 kD and/or 480 kD ankyrinG are components of the membrane undercoat of axons at the node of Ranvier. This paper focuses on definition of the isoforms of ankyrin-binding cell adhesion molecules localized with ankyrinG at the nodal axon segment. The exon usage of two major forms of neurofascin was determined by isolation of full-length cDNAs and used to prepare isoform-specific antibodies. An isoform of neurofascin containing a mucin-like domain and lacking the third FNIII domain was concentrated at axon initial segments and colocalized at nodes of Ranvier with ankyrinG and the voltage-dependent sodium channel. An alternative form of neurofascin lacking the mucin-like domain and containing the third FNIII domain was present in unmyelinated axons. The antibody initially raised against neurofascin was used to screen a rat brain cDNA expression library. In addition to neurofascin, this screen yielded a clone with 80% sequence identity to NrCAM from chicken. The sequences of two full-length cDNAs are presented. NrCAM is most closely related to neurofascin among the other members of the L1/neurofascin/NgCAM family, with over 70% identity between cytoplasmic domains. NrCAM, visualized with antibodies specific for the ecto-domain, also was found to be coexpressed with neurofascin at nodes of Ranvier and at axon initial segments. This is the first characterization of defined neuronal cell adhesion molecules localized to axonal membranes at the node of Ranvier of myelinated axons.

Immuno-ultrastructural localization of sodium channels at nodes of Ranvier and perinodal astrocytes in rat optic nerve

1989 ◽  
Vol 238 (1290) ◽  
pp. 39-51 ◽  
Keyword(s):  
Optic Nerve ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Node Of Ranvier ◽  
Ultrastructural Localization ◽  
Active Role ◽  
Nodes Of Ranvier ◽  
Electron Microscopic ◽  
Axon Membrane ◽  
Intense Immunoreactivity

Immuno-electron microscopic localization of sodium channels at nodes of Ranvier within adult optic nerve was demonstrated with polyclonal antibody 7493. The 7493 antisera, which is directed against purified sodium channels from rat brain, recognizes a 260 kDa protein in immunoblots of the crude glycoprotein fraction from adult rat optic nerve. Intense immunoreactivity with 7493 antisera was observed at nodes of Ranvier. Axon membrane at the node was densely stained, whereas paranodal and internodal axon membrane did not exhibit immunoreactivity. The axoplasm beneath the nodal membrane displayed variable immunostaining. Neither terminal paranodal oligodendroglial loops nor oligodendrocyte plasmalemma were immunoreactive with 7493 antisera. However, perinodal astrocyte processes exhibited intense immunoreactivity with the anti-sodium channel antisera. Optic nerves incubated with pre-immune sera, or with 7493 antisera that had been pre-adsorbed with purified sodium channel protein, displayed no immunoreactivity. These results demonstrate localization of sodium channels at high density at mammalian nodes of Ranvier and in some perinodal astrocyte processes. The latter observation offers support for an active role for perinodal astrocyte processes in the aggregation of sodium channels within the axon membrane at the node of Ranvier.

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