Faculty Opinions recommendation of Maintenance of axo-oligodendroglial paranodal junctions requires DCC and netrin-1.

2008 ◽  
Author(s):  
Elior Peles
Keyword(s):  
Paranodal Junctions

scholarly journals Mechanical Stretch of High Magnitude Provokes Axonal Injury, Elongation of Paranodal Junctions, and Signaling Alterations in Oligodendrocytes

2018 ◽  
Vol 56 (6) ◽  
pp. 4231-4248 ◽  
Author(s):  
Elena Chierto ◽  
Anne Simon ◽  
Francesca Castoldi ◽  
Delphine Meffre ◽  
Giulia Cristinziano ◽  
...  
Keyword(s):  
Axonal Injury ◽  
Mechanical Stretch ◽  
High Magnitude ◽  
Paranodal Junctions

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 Progressive Disorganization of Paranodal Junctions and Compact Myelin Due to Loss of DCC Expression by Oligodendrocytes

2014 ◽  
Vol 34 (29) ◽  
pp. 9768-9778 ◽  
Author(s):  
S.-J. Bull ◽  
J. M. Bin ◽  
E. Beaumont ◽  
A. Boutet ◽  
P. Krimpenfort ◽  
...  
Keyword(s):  
Paranodal Junctions

Septate and paranodal junctions: kissing cousins

2003 ◽  
Vol 13 (11) ◽  
pp. 557-561 ◽  
Author(s):  
Michael Hortsch ◽  
Ben Margolis
Keyword(s):  
Paranodal Junctions

scholarly journals Absence of Axoglial Paranodal Junctions in a Child With CNTNAP1 Mutations, Hypomyelination, and Arthrogryposis

2018 ◽  
Vol 33 (10) ◽  
pp. 642-650 ◽  
Author(s):  
Alexander Conant ◽  
Julian Curiel ◽  
Amy Pizzino ◽  
Parisa Sabetrasekh ◽  
Jennifer Murphy ◽  
...  
Keyword(s):  
Quadriceps Muscle ◽  
Magnetic Resonance Images ◽  
Compound Heterozygous ◽  
Arthrogryposis Multiplex Congenita ◽  
Axonal Pathology ◽  
Whole Exome ◽  
Paranodal Junctions ◽  
Biallelic Mutations ◽  
Congenital Hypomyelinating Neuropathy ◽  
Muscle Biopsies

Leukodystrophies and genetic leukoencephalopathies are a heterogeneous group of heritable disorders that affect the glial-axonal unit. As more patients with unsolved leukodystrophies and genetic leukoencephalopathies undergo next generation sequencing, causative mutations in genes leading to central hypomyelination are being identified. Two such individuals presented with arthrogryposis multiplex congenita, congenital hypomyelinating neuropathy, and central hypomyelination with early respiratory failure. Whole exome sequencing identified biallelic mutations in the CNTNAP1 gene: homozygous c.1163G>C (p.Arg388Pro) and compound heterozygous c.967T>C (p.Cys323Arg) and c.319C>T (p.Arg107*). Sural nerve and quadriceps muscle biopsies demonstrated progressive, severe onion bulb and axonal pathology. By ultrastructural evaluation, septate axoglial paranodal junctions were absent from nodes of Ranvier. Serial brain magnetic resonance images revealed hypomyelination, progressive atrophy, and reduced diffusion in the globus pallidus in both patients. These 2 families illustrate severe progressive peripheral demyelinating neuropathy due to the absence of septate paranodal junctions and central hypomyelination with neurodegeneration in CNTNAP1-associated arthrogryposis multiplex congenita.

scholarly journals Contactin-Associated Protein (Caspr) and Contactin Form a Complex That Is Targeted to the Paranodal Junctions during Myelination

2000 ◽  
Vol 20 (22) ◽  
pp. 8354-8364 ◽  
Author(s):  
Jose C. Rios ◽  
Carmen V. Melendez-Vasquez ◽  
Steven Einheber ◽  
Marc Lustig ◽  
Martin Grumet ◽  
...  
Keyword(s):  
Paranodal Junctions

scholarly journals CNTNAP1 mutations cause CNS hypomyelination and neuropathy with or without arthrogryposis

2017 ◽  
Vol 3 (2) ◽  
pp. e144 ◽  
Author(s):  
Holger Hengel ◽  
Alex Magee ◽  
Muhammad Mahanjah ◽  
Jean-Michel Vallat ◽  
Robert Ouvrier ◽  
...  
Keyword(s):  
Brain Mri ◽  
Cerebellar Atrophy ◽  
Nerve Biopsy ◽  
Compound Heterozygous ◽  
Arthrogryposis Multiplex Congenita ◽  
Whole Exome ◽  
Paranodal Junctions ◽  
Distinct Features ◽  
Deep Phenotyping

Objective:To explore the phenotypic spectrum and pathophysiology of human disease deriving from mutations in the CNTNAP1 gene.Methods:In a field study on consanguineous Palestinian families, we identified 3 patients carrying homozygous mutations in the CNTNAP1 gene using whole-exome sequencing. An unrelated Irish family was detected by screening the GENESIS database for further CNTNAP1 mutations. Neurophysiology, MRI, and nerve biopsy including electron microscopy were performed for deep phenotyping.Results:We identified 3 novel CNTNAP1 mutations in 5 patients from 2 families: c.2015G>A:p.(Trp672*) in a homozygous state in family 1 and c.2011C>T:p.(Gln671*) in a compound heterozygous state with c.2290C>T:p.(Arg764Cys) in family 2. Affected patients suffered from a severe CNS disorder with hypomyelinating leukodystrophy and peripheral neuropathy of sensory-motor type. Arthrogryposis was present in 2 patients but absent in 3 patients. Brain MRI demonstrated severe hypomyelination and secondary cerebral and cerebellar atrophy as well as a mega cisterna magna and corpus callosum hypoplasia. Nerve biopsy revealed very distinct features with lack of transverse bands at the paranodes and widened paranodal junctional gaps.Conclusions:CNTNAP1 mutations have recently been linked to patients with arthrogryposis multiplex congenita. However, we show that arthrogryposis is not an obligate feature. CNTNAP1-related disorders are foremost severe hypomyelinating disorders of the CNS and the peripheral nervous system. The pathology is partly explained by the involvement of CNTNAP1 in the proper formation and preservation of paranodal junctions and partly by the assumed role of CNTNAP1 as a key regulator in the development of the cerebral cortex.

scholarly journals Maintenance of Axo-Oligodendroglial Paranodal Junctions Requires DCC and Netrin-1

2008 ◽  
Vol 28 (43) ◽  
pp. 11003-11014 ◽  
Author(s):  
A. A. Jarjour ◽  
S.-J. Bull ◽  
M. Almasieh ◽  
S. Rajasekharan ◽  
K. A. Baker ◽  
...  
Keyword(s):  
Paranodal Junctions

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

2006 ◽  
Vol 2 (3) ◽  
pp. 165-174 ◽  
Author(s):  
STEVEN EINHEBER ◽  
MANZOOR A. BHAT ◽  
JAMES L. SALZER
Keyword(s):  
Energy Metabolism ◽  
Peripheral Nerves ◽  
Physiological Role ◽  
Myelinated Axons ◽  
Local Regulation ◽  
Nodal Region ◽  
Paranodal Junctions ◽  
Abnormal Mitochondria ◽  
Sciatic Nerves ◽  
And Function

Mitochondria and other membranous organelles are frequently enriched in the nodes and paranodes of peripheral myelinated axons, particularly of large caliber axons. The physiological role(s) of this organelle enrichment and the rheologic factors that regulate it are not well understood. Previous studies indicate that axonal transport of organelles across the nodal/paranodal region is regulated locally. In this study, we have examined the ultrastructure of myelinated axons in the sciatic nerves of mice deficient in 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. Typically, these mitochondria are large, swollen and occupy prominent varicosities of the nodal axolemma. In contrast, mitochondria 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 indicate that paranodal junctions might have a role, either direct or indirect, in the local regulation of energy metabolism in the nodal region.

scholarly journals Focal Loss of the Paranodal Domain Protein Neurofascin155 in the Internal Capsule Impairs Cortically Induced Muscle Activity in Vivo.

2020 ◽  
Author(s):  
Kazuo Kunisawa ◽  
Nobuhiko Hatanaka ◽  
Takeshi Shimizu ◽  
Kenta Kobayashi ◽  
Yasuyuki Osanai ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Internal Capsule ◽  
Triceps Brachii ◽  
Myelinated Axons ◽  
Electrophysiological Properties ◽  
Motor Behaviors ◽  
Paranodal Junctions ◽  
The Central Nervous System ◽  
The Impact

Abstract Paranodal axoglial junctions are essential for rapid nerve conduction and the organization of axonal domains in myelinated axons. Neurofascin155 (Nfasc155) is a glial cell adhesion molecule that is also required for the assembly of these domains. Previous studies have demonstrated that general ablation of Nfasc155 disorganizes these domains, reduces conduction velocity, and disrupts motor behaviors. Multiple sclerosis (MS), a typical disorder of demyelination in the central nervous system, is reported to have autoantibody to Nfasc155. However, the impact of focal loss of Nfasc155, which may occur in MS patients, remains unclear. Here, we examined whether restricted focal loss of Nfasc155 affects the electrophysiological properties of the motor system in vivo. Adeno-associated virus type5 (AAV5) harboring EGFP-2A-Cre was injected into the glial-enriched internal capsule of floxed-Neurofascin (NfascFlox/Flox) mice to focally disrupt paranodal junctions in the cortico-fugal fibers from the motor cortex to the spinal cord. Electromyograms (EMGs) of the triceps brachii muscles in response to electrical stimulation of the motor cortex were successively examined in these awake mice. EMG analysis showed significant delay in the onset and peak latencies after AAV injection compared to control (Nfasc+/+) mice. Moreover, EMG half-widths were increased, and EMG amplitudes were gradually decreased by 13 weeks. Similar EMG changes have been reported in MS patients. These findings provide physiological evidence that motor outputs are obstructed by focal ablation of paranodal junctions in myelinated axons. Our findings may open a new path toward development of a novel biomarker for an early phase of human MS, as Nfasc155 detects microstructural changes in the paranodal junction.

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