Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor

  title={Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor},
  author={Betty P. Liu and Alyson E. Fournier and Tadzia Grandpr{\'e} and Stephen M. Strittmatter},
  pages={1190 - 1193}
Axonal regeneration in the adult central nervous system (CNS) is limited by two proteins in myelin, Nogo and myelin-associated glycoprotein (MAG). The receptor for Nogo (NgR) has been identified as an axonal glycosyl-phosphatidyl-inositol (GPI)–anchored protein, whereas the MAG receptor has remained elusive. Here, we show that MAG binds directly, with high affinity, to NgR. Cleavage of GPI-linked proteins from axons protects growth cones from MAG-induced collapse, and dominant-negative NgR… 

p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp

Interference with p75 and its downstream signalling pathways may allow lesioned axons to overcome most of the inhibitory activities associated with central nervous system myelin.

A p75NTR and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein

It is reported that the p75 neurotrophin receptor (p75NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target for promoting nerve regeneration.

Myelin‐associated glycoprotein and its axonal receptors

The findings and challenges in associating MAG's biological effects with specific receptors are reviewed, sialoglycans (specifically gangliosides GD1a and GT1b and Nogo receptors (NgRs) are described, and controversies remain about which receptor(s) mediates which of MAG's Biological effects.

The Nogo-66 Receptor Homolog NgR2 Is a Sialic Acid-Dependent Receptor Selective for Myelin-Associated Glycoprotein

It is shown that NgR2 is a novel receptor for MAG and acts selectively to mediate MAG inhibitory responses and provide insights into how interactions between MAG and members of the Nogo receptor family function to coordinate myelin inhibitsory responses.

Myelin-associated glycoprotein-mediated signaling in central nervous system pathophysiology

New findings in MAG-forward and-reverse signaling and its role in CNS pathophysiology are discussed.

NgR acts as an inhibitor to axonal regeneration in adults.

One avenue for promotion of axonal regeneration is by virtue of blocking the inhibitory effects of NgR, which binds to the same neuronal glycosylphosphatidylinositol-anchored receptors (NgR) and transduce inhibitory signals to cells by the transmembrane co-receptor, p75.

Myelin‐associated glycoprotein (MAG): past, present and beyond

The myelin‐associated glycoprotein contains a carbohydrate epitope shared with other glycoconjugates that is a target antigen in autoimmune peripheral neuropathy associated with IgM gammopathy and has been implicated in a dying back oligodendrogliopathy in multiple sclerosis.

Gangliosides and Nogo Receptors Independently Mediate Myelin-associated Glycoprotein Inhibition of Neurite Outgrowth in Different Nerve Cells*

The data indicate that MAG inhibits axon outgrowth via two independent receptors, gangliosides and NgRs, and that in DRGNs, dMAG inhibition was exclusively NgR-dependent, whereas in CGNs it was exclusively Ganglioside-dependent.

PirB is a Functional Receptor for Myelin Inhibitors of Axonal Regeneration

This work has found that paired immunoglobulin-like receptor B (PirB), which has been implicated in nervous system plasticity, is a high-affinity receptor for Nogo, MAG, and OMgp, and partially rescues neurite inhibition by Nogo66,MAG, OM gp, and myelin in cultured neurons.



Nogo-66 receptor antagonist peptide promotes axonal regeneration

The Nogo-66(1–40) antagonist peptide (NEP1-40) blocks Nogo or CNS myelin inhibition of axonal outgrowth in vitro, demonstrating that NgR mediates a significant portion of axon outgrowth inhibition by myelin.

Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration

It is shown that the extracellular domain of Nogo (Nogo-66) inhibits axonal extension, but does not alter non-neuronal cell morphology, and a multivalent form of the N terminus of Noga-A affects the morphology of both neurons and other cell types.

Localization of Nogo-A and Nogo-66 Receptor Proteins at Sites of Axon–Myelin and Synaptic Contact

Data confirm the apposition of Nogo ligand and NgR receptor in situations of limited axonal regeneration and support the hypothesis that this system regulates CNS axonal plasticity and recovery from injury.

Gangliosides are neuronal ligands for myelin-associated glycoprotein.

  • L. J. YangC. Zeller R. Schnaar
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
It is reported that a limited set of structurally related gangliosides, known to be expressed on myelinated neurons in vivo, are ligands for MAG, consistent with the conclusion that MAG-mediated cell-cell interactions involve MAG-ganglioside recognition and binding.

Myelin-associated Glycoprotein Interacts with Neurons via a Sialic Acid Binding Site at ARG118 and a Distinct Neurite Inhibition Site

It is shown that myelin-associated glycoprotein's sialic acid binding site is distinct from its neurite inhibitory activity, suggesting that a second site must exist on MAG which elicits this response.

Myelin-associated Glycoprotein Interacts with Ganglioside GT1b

Evidence is presented to suggest that recognition of sialylated glycans is essential for inhibition of neurite outgrowth by MAG and interaction with GT1b on the neuronal cell surface is a potential mechanism for inhibition.

Nogo-A, a Potent Inhibitor of Neurite Outgrowth and Regeneration

Nogo-A is a high molecular weight transmembrane protein and an antigen of the monoclonal antibody mAb IN-1 that was shown to promote long-distance regeneration and functional recovery in vivo when applied to spinal cord-injured adult rats.

Myelin‐associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse

In vitro studies provide the first evidence that MAG modulates growth cone behavior and inhibits neurite growth by causing growth cone collapse.