LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex

  title={LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex},
  author={Sha Mi and Xinhua Lee and Zhaohui Shao and Gregory Patrick Thill and Benxiu Ji and Jane K. Relton and M{\'e}lissa L{\'e}vesque and Norm Allaire and S. Perrin and Bryan Sands and Tom Crowell and Richard L. Cate and John M. Mccoy and R. Blake Pepinsky},
  journal={Nature Neuroscience},
Axon regeneration in the adult CNS is prevented by inhibitors in myelin. These inhibitors seem to modulate RhoA activity by binding to a receptor complex comprising a ligand-binding subunit (the Nogo-66 receptor NgR1) and a signal transducing subunit (the neurotrophin receptor p75). However, in reconstituted non-neuronal systems, NgR1 and p75 together are unable to activate RhoA, suggesting that additional components of the receptor may exist. Here we describe LINGO-1, a nervous system-specific… 
LINGO-1 Protein Interacts with the p75 Neurotrophin Receptor in Intracellular Membrane Compartments*
It is found that endogenous LINGO-1 expression in neurons in the cortex and cerebellum is intracellular and co-immunoprecipitation experiments demonstrated that Lingo-1 and NgR competed for binding to p75NTR in a manner that is difficult to reconcile with the existence of a cell-surface ternary complex.
From Cell Death to Neuronal Regeneration, Effects of the p75 Neurotrophin Receptor Depend on Interactions with Partner Subunits
The results of Mi et al. indicate that p75NTR exerts its diverse cellular functions by associating with function-specific co-receptors.
Molecular dissection of the myelin-associated glycoprotein receptor complex reveals cell type–specific mechanisms for neurite outgrowth inhibition
It is found that VCN treatment is not sufficient to releaseMAG inhibition of RGCs; however, it does attenuate MAG inhibition of cerebellar granule neurons, and distinct and cell type–specific mechanisms for MAG-elicited growth inhibition are revealed.
Targeting the Nogo receptor complex in diseases of the central nervous system.
Three examples will be used: blocking of ligand binding to NgR1 in treatment of spinal cord injury, antibody-mediated inhibition of LINGO-1 to promote oligodendrocyte differentiation in multiple sclerosis, and the use of soluble NgR 1 to sequester Abeta peptide in the periphery in Alzheimer's disease.
Structural features of the Nogo receptor signaling complexes at the neuron/myelin interface
Ganglioside mediate the interaction between Nogo receptor 1 and LINGO-1.


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.
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.
The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI
It is shown that direct interaction of the Rho GDP dissociation inhibitor (Rho-GDI) with p75NTR initiates the activation of RhoA, and this interaction between p 75NTR and Rho- GDI is strengthened by MAG or Nogo, which has potential as a therapeutic agent against the inhibitory cues that block regeneration in the central nervous system.
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.
Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor
It is shown that MAG binds directly, with high affinity, to NgR, and Cleavage of GPI-linked proteins from axons protects growth cones from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of neurite outgrowth.
The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho
It is shown that the neurotrophin receptor p75 (p75NTR) is the signal transducing element for myelin-associated glycoprotein (MAG), and Ganglioside GT1b, which is one of the binding partners of MAG, specifically associates with p75N TR, which may form a receptor complex for MAG to transmit the inhibitory signals in neurons.
Structure and axon outgrowth inhibitor binding of the Nogo‐66 receptor and related proteins
It is shown that the binding of soluble fragments of Nogo, MAG and NgR to cell‐surface NgR requires the entire leucine‐rich repeat (LRR) region of NgR, but not other portions of the protein.
Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1
Cl cloning of nogo A, the rat complementary DNA encoding NI-220/250 is reported, showing that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.
The Nogo receptor, its ligands and axonal regeneration in the spinal cord; A review
It is not clear whether antibodies against Nogo act on oligodendrocytes/myelin or by binding to neuronal Nogo, or whether they can stimulate regeneration of ascending axons in the spinal cord, most of which express little or no NgR.