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Wong, S.T. et al. A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat. Neurosci. 5, 1302-1308

Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Nature Neuroscience (Impact Factor: 14.98). 01/2003; 5(12):1302-8. DOI: 10.1038/nn975
Source: PubMed

ABSTRACT Myelin-associated glycoprotein (MAG), an inhibitor of axon regeneration, binds with high affinity to the Nogo-66 receptor (NgR). Here we report that the p75 neurotrophin receptor (p75(NTR)) is a co-receptor of NgR for MAG signaling. In cultured human embryonic kidney (HEK) cells expressing NgR, p75(NTR) was required for MAG-induced intracellular Ca2+ elevation. Co-immunoprecipitation showed an association of NgR with p75(NTR) that can be disrupted by an antibody against p75(NTR) (NGFR5), and extensive coexpression was observed in the developing rat nervous system. Furthermore, NGFR5 abolished MAG-induced repulsive turning of Xenopus axonal growth cones and Ca2+ elevation, both in neurons and in NgR/p75(NTR)-expressing HEK cells. Thus we conclude that p75(NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target for promoting nerve regeneration.

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    • "The adult mammalian central nervous system (CNS) cannot be repaired spontaneously after injury. The lack of regenerative capacity in the mammalian CNS is partly due to the myelin-associated proteins including Nogo-A1, myelin-associated glycoprotein23 and oligodendrocyte myelin glycoprotein45. Nogo-66 receptor 1 (NgR1) is a common receptor for the myelin-associated inhibitors of the regeneration (i.e., Nogo-A, myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein)6, as well as chondroitin sulphate proteoglycans7. Inhibition of NgR activation with neutralising antibodies against Nogo-A8, a peptide mimicking NgR1-binding region of Nogo-A (NEP1-40)9 or the ecto-domain part of NgR1 (NgR1(310) ecto-Fc)10, can promote functional recovery of the spinal cord after traumatic injury. "
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    • "Nogo-66 is a 66 amino acid domain that, together with flanking hydrophobic regions, is a component of the RTN homology domain in the C-terminus of all Nogo isoforms [6]. Nogo-66 collapse-inducing activity is associated with high-affinity binding to its receptors NgR1 [7], [8], which forms a complex with the transmembrane proteins LINGO1, and p75 or TROY [1], [9]–[11]. Nogo-66 can also bind to the paired immunoglobulin-like receptor PirB [11]. "
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    • "Interactions between trk receptors and voltage-gated potassium channels or NMDA receptors have been described [20,21]. The p75NTR can act as a co-receptor for the Nogo receptor that is known to inhibit axonal growth by interactions with MAG protein [22,23]. "
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