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

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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Available from: John R Henley, Jul 08, 2015
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    • "The neuronal transmembrane co-receptors uncovered so far include the nerve growth factor (Ngf) receptor (Ngfr, otherwise known as Lngfr, Tnfrsf16, p75, or p75NTR), Troy (or Taj, Tnfrsf19), which are members of the tumor necrosis factor receptor (Tnfr) family, and Lingo1. P75 was found to interact with NgR by forming a receptor complex [8] [10] and p75-mutant mice displayed drastically decreased responses to Nogo, MAG and OMgp [8] [11]. However, most mature neurons do not express p75 [12]. "
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    • "Knocking-down of p75NTR in myocytes using a morpholino specifically against Xenopus p75NTR (p75NTR-Mo) significantly attenuated BDNF-induced synaptic potentiation of the frequency of spontaneous PSCs at the NMJ (p = 0.01; Fig. 7B & D; control: interevent interval: 6.1 ± 1.4 s before BDNF and 0.9 ± 0.2 s after BDNF, n = 10; p75NTR-Mo: interevent interval: 8.5 ± 1.9 s before BDNF and 3.6 ± 1.0 s after BDNF, n = 16). A similar effect was observed after pre-incubating cultures with NGFR5 (5 μg/ml; p = 0.01; Fig. 7B & D; interevent interval: 7.1 ± 1.5 s before BDNF and 3.3 ± 1.0 s after BDNF; n = 9), a function-blocking antibody that has been previously shown to suppress p75NTR function in Xenopus spinal cultures (Wong et al., 2002). In contrast, pre-incubation with a control IgG antibody (5 μg/ml) did not affect BDNF-induced synaptic potentiation of the frequency of spontaneous PSCs at the NMJ (p = 0.44; Fig. 7B & D; interevent interval: 9.5 ± 1.7 s before BDNF and 2.0 ± 0.6 s after BDNF; n = 16). "
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