Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186

Koticha, Darshan; Babiarz, Joanne; Kane‐Goldsmith, Noriko; Jacob, Jeffrey; Raju, Karthik; Grumet, Martin

doi:10.1016/j.mcn.2005.06.007

Cited by 37 publications

(21 citation statements)

References 43 publications

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“…Neurofascin Overexpression Modulates Gephyrin Clustering in Hippocampal Neurons-Two functionally distinct neuronal neurofascin isoforms are found in brain, mainly differing in the expression of the fifth FNIII-like repeat which is absent in NF166 (NF Ϫ5.FNIII ) and present in NF186 (NF ϩ5.FNIII ) (19,24). Analysis of the expression of neurofascin in rat brain revealed (Fig.…”

Section: L O P S and T)mentioning

confidence: 98%

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

Kriebel

Metzger

Trinks

et al. 2011

Journal of Biological Chemistry

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Cell adhesion molecules regulate synapse formation and maintenance via transsynaptic contact stabilization involving both extracellular interactions and intracellular postsynaptic scaffold assembly. The cell adhesion molecule neurofascin is localized at the axon initial segment of granular cells in rat dentate gyrus, which is mainly targeted by chandelier cells. Lentiviral shRNA-mediated knockdown of neurofascin in adult rat brain indicates that neurofascin regulates the number and size of postsynaptic gephyrin scaffolds, the number of GABA A receptor clusters as well as presynaptic glutamate decarboxylase-positive terminals at the axon initial segment. By contrast, overexpression of neurofascin in hippocampal neurons increases gephyrin cluster size presumably via stimulation of fibroblast growth factor receptor 1 signaling pathways.

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Section: L O P S and T)mentioning

confidence: 98%

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

Kriebel

Metzger

Trinks

et al. 2011

Journal of Biological Chemistry

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“…13 Nonetheless, NF155 has been found to favor the cell adhesion of Schwann cells or dorsal root ganglion neurons, notably through the Fn3 domain. 21 Thus, this domain may bind glial/axonal partners and have a role in paranode formation or its stability.…”

Section: Association Of Cidp With Anti-nf155 Igg4 Antibodiesmentioning

confidence: 99%

Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy

et al. 2016

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Objective: We report the clinical and serologic features of Japanese patients with chronic inflammatory demyelinating polyneuropathy (CIDP) displaying anti-neurofascin-155 (NF155) immunoglobulin G4 (IgG4) antibodies. Methods:In sera from 533 patients with CIDP, anti-NF155 IgG4 antibodies were detected by ELISA. Binding of IgG antibodies to central and peripheral nerves was tested.Results: Anti-NF155 IgG4 antibodies were identified in 38 patients (7%) with CIDP, but not in disease controls or normal participants. These patients were younger at onset as compared to 100 anti-NF155-negative patients with CIDP. Twenty-eight patients (74%) presented with sensory ataxia, 16 (42%) showed tremor, 5 (13%) presented with cerebellar ataxia associated with nystagmus, 3 (8%) had demyelinating lesions in the CNS, and 20 of 25 (80%) had poor response to IV immunoglobulin. The clinical features of the antibody-positive patients were statistically more frequent as compared to negative patients with CIDP (n 5 100). Anti-NF155 IgG antibodies targeted similarly central and peripheral paranodes.Conclusion: Anti-NF155 IgG4 antibodies were associated with a subgroup of patients with CIDP showing a younger age at onset, ataxia, tremor, CNS demyelination, and a poor response to IV immunoglobulin. The autoantibodies may serve as a biomarker to improve patients' diagnosis and guide treatments. Neurology ® 2016;86:800-807 GLOSSARY Caspr1 5 contactin-associated protein-1; CCPD 5 combined central and peripheral demyelination; CI 5 confidence interval; CIDP 5 chronic inflammatory demyelinating polyneuropathy; CNTN1 5 contactin 1; GBS 5 Guillain-Barré syndrome; IgG4 5 immunoglobulin G4; IVIg 5 IV immunoglobulin; MS 5 multiple sclerosis; NF155 5 neurofascin-155; OR 5 odds ratio; PNS 5 peripheral nervous system.Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired immune-mediated neuropathy worldwide and is clinically heterogeneous.1 Proven treatments for CIDP include corticosteroids, plasma exchange, and IV immunoglobulin (IVIg). However, the response rates to treatments are highly heterogeneous between patients. This emphasizes that patients and clinicians require biomarkers to identify CIDP subgroups and guide specific immunotherapeutic options.Immunoglobulin G4 (IgG4) autoantibodies to neurofascin-155 (NF155) were recently documented in patients with CIDP.2,3 NF155 belongs to the L1 family of adhesion molecules and is expressed at paranodes by the terminal loops of myelin and associates with the axonal cell adhesion molecules CNTN1 and contactin-associated protein-1 (Caspr1). 4 This ternary complex of glycoproteins is required for the rapid propagation of the nerve impulses along myelinated axons. 5,6 Three of 4 patients with anti-NF155 IgG4 showed disabling tremor and all showed poor response to IVIg. 3 This suggested that IgG4 autoantibodies participate in CIDP pathogenesis; nonetheless, the low number of reactive patients precluded statistical correlation.

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“…NF155 and NF186 have different expression patterns and probably different functions, e.g. neurite outgrowth is promoted by NF155 but inhibited by NF186 (15).…”

mentioning

confidence: 99%

Homophilic Adhesion Mechanism of Neurofascin, a Member of the L1 Family of Neural Cell Adhesion Molecules

Liu

Focia

2011

Journal of Biological Chemistry

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The L1 family neural cell adhesion molecules play key roles in specifying the formation and remodeling of the neural network, but their homophilic interaction that mediates adhesion is not well understood. We report two crystal structures of a dimeric form of the headpiece of neurofascin, an L1 family member. The four N-terminal Ig-like domains of neurofascin form a horseshoe shape, akin to several other immunoglobulin superfamily cell adhesion molecules such as hemolin, axonin, and Dscam. The neurofascin dimer, captured in two crystal forms with independent packing patterns, reveals a pair of horseshoes in trans-synaptic adhesion mode. The adhesion interaction is mediated mostly by the second Ig-like domain, which features an intermolecular ␤-sheet formed by the joining of two individual GFC ␤-sheets and a large but loosely packed hydrophobic cluster. Mutagenesis combined with gel filtration assays suggested that the side chain hydrogen bonds at the intermolecular ␤-sheet are essential for the homophilic interaction and that the residues at the hydrophobic cluster play supplementary roles. Our structures reveal a conserved homophilic adhesion mode for the L1 family and also shed light on how the pathological mutations of L1 affect its structure and function.

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Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186

Cited by 37 publications

References 43 publications

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy

Homophilic Adhesion Mechanism of Neurofascin, a Member of the L1 Family of Neural Cell Adhesion Molecules

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