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Gene Review

Ngfr  -  nerve growth factor receptor (TNFR...

Mus musculus

Synonyms: LNGFR, Low affinity neurotrophin receptor p75NTR, Low-affinity nerve growth factor receptor, NGF receptor, Tnfrsf16, ...
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Disease relevance of Ngfr


Psychiatry related information on Ngfr


High impact information on Ngfr

  • Interestingly, final target-derived NGF promotes expression of the p75 neurotrophin receptor, in turn causing a reduction in the sensitivity of axons to intermediate target-derived NT-3 [9].
  • NGF was constitutively produced by B cells only, which also expressed surface p140trk-A and p75NGFR molecules and hence efficiently bound and internalized the cytokine [10].
  • Our results suggest that p75NGFR has an important role in the development and function of sensory neurons [11].
  • The mutation in the gene encoding p75NGFR did not decrease the size of sympathetic ganglia or the density of sympathetic innervation of the iris or salivary gland [11].
  • Crossing a human transgene encoding p75NGFR into the mutant animals rescued the absent heat sensitivity and the occurrence of skin ulcers and increased the density of neuropeptide-immunoreactive sensory innervation of footpad skin [11].

Chemical compound and disease context of Ngfr


Biological context of Ngfr


Anatomical context of Ngfr

  • It was revealed that the growth of the esophageal epithelium begins from postnatal day 3, and that the timing is consistent with membrane localization of Ngfr in the basal cell [21].
  • The LNGFR is not expressed in our fibroblast system, implying that this receptor is not essential for responses to physiological concentrations of the neurotrophins [22].
  • This activation was not observed in Schwann cells isolated from mice that lacked p75NTR [23].
  • Neuron number is normal in sympathetic ganglia of adult p75NTR-/- mice [24].
  • We demonstrate that ephrin-B3 is expressed in postnatal myelinating oligodendrocytes and, by using primary CNS neurons, show that ephrin-B3 accounts for an inhibitory activity equivalent to that of the other three myelin-based inhibitors, acting through p75, combined [25].

Associations of Ngfr with chemical compounds

  • These factors utilize the Trk family of receptor tyrosine kinases, perhaps in conjunction with a second component known as the low affinity NGF receptor (LNGFR) [22].
  • After 4 weeks of streptozotocin-induced diabetes, the number of immunoreactive CGRP A-cells was reduced from 692 +/- 122 to 489 +/- 125 (P = 0.004) in p75(+/+) mice on the noncrushed side [26].
  • Sciatic nerve crush was associated with a substantial loss of L5DRG B-cells in diabetic and nondiabetic p75(+/+) mice and with substantial loss of immunoreactive substance P cells in diabetic p75(+/+) mice [26].
  • The p75NTR-dependent effect requires NGF (nerve growth factor) binding and activation of the second messenger ceramide [27].
  • The low affinity receptor (Kd approximately 10(-9) to 10(-8) M) is a cysteine-rich glycoprotein encoded by the previously characterized LNGFR gene [28].

Physical interactions of Ngfr

  • Surprisingly, most sets of trkA-dependent sensory innervation are suppressed by trkB perhaps interacting with p75 [29].
  • The p75 neurotrophin receptor has been implicated in neurotrophin binding and signaling for both NGF and NT3 [30].
  • The zinc finger protein NRIF (neurotrophin receptor interacting factor) was originally identified by virtue of its interaction with the neurotrophin receptor p75NTR and its participation in embryonic apoptosis [31].
  • In contrast, brain-derived neurotrophic factor (BDNF) binding to p75 resulted in an equivalent level of apoptosis in neurons expressing Cre, GFP, and uninfected cells [32].
  • We have previously shown that dendrite morphology of cultured hippocampal neurones is controlled by Notch receptor activation or binding of nerve growth factor (NGF) to its low affinity receptor p75NTR, i.e. processes that up-regulate the expression of the Homologue of enhancer of split 1 and 5 [33].

Regulatory relationships of Ngfr


Other interactions of Ngfr

  • Blockade of p75NTR prevented bFGF reduction and resulted in both structural and functional photoreceptor survival in vivo [1].
  • Function-blocking antibody studies indicate that this apoptosis is due to BDNF-mediated activation of p75NTR [38].
  • Involvement of transcription factor encoded by the mouse mi locus (MITF) in expression of p75 receptor of nerve growth factor in cultured mast cells of mice [19].
  • In p75(-/-) mice, there was no such effect of diabetes on the immunoreactive CGRP A-cell number [26].
  • Neurotrophin receptor interacting factor (NRIF) is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor [39].

Analytical, diagnostic and therapeutic context of Ngfr


  1. Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration. Harada, T., Harada, C., Nakayama, N., Okuyama, S., Yoshida, K., Kohsaka, S., Matsuda, H., Wada, K. Neuron (2000) [Pubmed]
  2. p53 is essential for developmental neuron death as regulated by the TrkA and p75 neurotrophin receptors. Aloyz, R.S., Bamji, S.X., Pozniak, C.D., Toma, J.G., Atwal, J., Kaplan, D.R., Miller, F.D. J. Cell Biol. (1998) [Pubmed]
  3. Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid-beta peptides via p75NTR/PLAIDD. Hashimoto, Y., Kaneko, Y., Tsukamoto, E., Frankowski, H., Kouyama, K., Kita, Y., Niikura, T., Aiso, S., Bredesen, D.E., Matsuoka, M., Nishimoto, I. J. Neurochem. (2004) [Pubmed]
  4. Effect of p75 neurotrophin receptor antagonist on disease progression in transgenic amyotrophic lateral sclerosis mice. Turner, B.J., Murray, S.S., Piccenna, L.G., Lopes, E.C., Kilpatrick, T.J., Cheema, S.S. J. Neurosci. Res. (2004) [Pubmed]
  5. Characterization of the toxic mechanism triggered by Alzheimer's amyloid-beta peptides via p75 neurotrophin receptor in neuronal hybrid cells. Tsukamoto, E., Hashimoto, Y., Kanekura, K., Niikura, T., Aiso, S., Nishimoto, I. J. Neurosci. Res. (2003) [Pubmed]
  6. A role for p75 receptor in neurotrophin-3 functioning during the development of limb proprioception. Fan, G., Jaenisch, R., Kucera, J. Neuroscience (1999) [Pubmed]
  7. Trks and p75 genes are differentially expressed in the inner ear of human embryos. What may Trks and p75 null mutant mice suggest on human development? Vega, J.A., San José, I., Cabo, R., Rodriguez, S., Represa, J. Neurosci. Lett. (1999) [Pubmed]
  8. Binding of beta-amyloid to the p75 neurotrophin receptor induces apoptosis. A possible mechanism for Alzheimer's disease. Yaar, M., Zhai, S., Pilch, P.F., Doyle, S.M., Eisenhauer, P.B., Fine, R.E., Gilchrest, B.A. J. Clin. Invest. (1997) [Pubmed]
  9. A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Kuruvilla, R., Zweifel, L.S., Glebova, N.O., Lonze, B.E., Valdez, G., Ye, H., Ginty, D.D. Cell (2004) [Pubmed]
  10. Nerve growth factor is an autocrine survival factor for memory B lymphocytes. Torcia, M., Bracci-Laudiero, L., Lucibello, M., Nencioni, L., Labardi, D., Rubartelli, A., Cozzolino, F., Aloe, L., Garaci, E. Cell (1996) [Pubmed]
  11. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Lee, K.F., Li, E., Huber, L.J., Landis, S.C., Sharpe, A.H., Chao, M.V., Jaenisch, R. Cell (1992) [Pubmed]
  12. Rabies virus glycoprotein (RVG) is a trimeric ligand for the N-terminal cysteine-rich domain of the mammalian p75 neurotrophin receptor. Langevin, C., Jaaro, H., Bressanelli, S., Fainzilber, M., Tuffereau, C. J. Biol. Chem. (2002) [Pubmed]
  13. The role of the p75 neurotrophin receptor in the morphology of dorsal root ganglion cells in streptozotocin diabetic mice: effects of sciatic nerve crush. Jiang, Y., Jakobsen, J. Diabetologia (2004) [Pubmed]
  14. Effects of NGF on acetylcholine, acetyl-CoA metabolism, and viability of differentiated and non-differentiated cholinergic neuroblastoma cells. Szutowicz, A., Madziar, B., Pawełczyk, T., Tomaszewicz, M., Bielarczyk, H. J. Neurochem. (2004) [Pubmed]
  15. Nerve growth factor survival signaling in cultured hippocampal neurons is mediated through TrkA and requires the common neurotrophin receptor P75. Culmsee, C., Gerling, N., Lehmann, M., Nikolova-Karakashian, M., Prehn, J.H., Mattson, M.P., Krieglstein, J. Neuroscience (2002) [Pubmed]
  16. p75NTR independent oligodendrocyte death in cuprizone-induced demyelination in C57BL/6 mice. Copray, J.C., Küst, B.M., Mantingh-Otter, I., Boddeke, H.W. Neuropathol. Appl. Neurobiol. (2005) [Pubmed]
  17. A comprehensive genetic map of murine chromosome 11 reveals extensive linkage conservation between mouse and human. Buchberg, A.M., Brownell, E., Nagata, S., Jenkins, N.A., Copeland, N.G. Genetics (1989) [Pubmed]
  18. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Soppet, D., Escandon, E., Maragos, J., Middlemas, D.S., Reid, S.W., Blair, J., Burton, L.E., Stanton, B.R., Kaplan, D.R., Hunter, T. Cell (1991) [Pubmed]
  19. Involvement of transcription factor encoded by the mouse mi locus (MITF) in expression of p75 receptor of nerve growth factor in cultured mast cells of mice. Jippo, T., Morii, E., Tsujino, K., Tsujimura, T., Lee, Y.M., Kim, D.K., Matsuda, H., Kim, H.M., Kitamura, Y. Blood (1997) [Pubmed]
  20. NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR. Mukai, J., Hachiya, T., Shoji-Hoshino, S., Kimura, M.T., Nadano, D., Suvanto, P., Hanaoka, T., Li, Y., Irie, S., Greene, L.A., Sato, T.A. J. Biol. Chem. (2000) [Pubmed]
  21. Molecular profiles of the mouse postnatal development of the esophageal epithelium showing delayed growth start. Daiko, H., Isohata, N., Sano, M., Aoyagi, K., Ogawa, K., Kameoka, S., Yoshida, T., Sasaki, H. Int. J. Mol. Med. (2006) [Pubmed]
  22. TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor. Glass, D.J., Nye, S.H., Hantzopoulos, P., Macchi, M.J., Squinto, S.P., Goldfarb, M., Yancopoulos, G.D. Cell (1991) [Pubmed]
  23. Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75. Carter, B.D., Kaltschmidt, C., Kaltschmidt, B., Offenhäuser, N., Böhm-Matthaei, R., Baeuerle, P.A., Barde, Y.A. Science (1996) [Pubmed]
  24. The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo. Brennan, C., Rivas-Plata, K., Landis, S.C. Nat. Neurosci. (1999) [Pubmed]
  25. Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Benson, M.D., Romero, M.I., Lush, M.E., Lu, Q.R., Henkemeyer, M., Parada, L.F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  26. Selective loss of calcitonin gene-related Peptide-expressing primary sensory neurons of the a-cell phenotype in early experimental diabetes. Jiang, Y., Nyengaard, J.R., Zhang, J.S., Jakobsen, J. Diabetes (2004) [Pubmed]
  27. A TrkA-to-p75NTR molecular switch activates amyloid beta-peptide generation during aging. Costantini, C., Weindruch, R., Della Valle, G., Puglielli, L. Biochem. J. (2005) [Pubmed]
  28. The trk proto-oncogene encodes a receptor for nerve growth factor. Klein, R., Jing, S.Q., Nanduri, V., O'Rourke, E., Barbacid, M. Cell (1991) [Pubmed]
  29. Differential dependency of unmyelinated and A delta epidermal and upper dermal innervation on neurotrophins, trk receptors, and p75LNGFR. Rice, F.L., Albers, K.M., Davis, B.M., Silos-Santiago, I., Wilkinson, G.A., LeMaster, A.M., Ernfors, P., Smeyne, R.J., Aldskogius, H., Phillips, H.S., Barbacid, M., DeChiara, T.M., Yancopoulos, G.D., Dunne, C.E., Fundin, B.T. Dev. Biol. (1998) [Pubmed]
  30. Levels of nerve growth factor and neurotrophin-3 are affected differentially by the presence of p75 in sympathetic neurons in vivo. Harrison, S.M., Jones, M.E., Uecker, S., Albers, K.M., Kudrycki, K.E., Davis, B.M. J. Comp. Neurol. (2000) [Pubmed]
  31. Strain-specific complementation between NRIF1 and NRIF2, two zinc finger proteins sharing structural and biochemical properties. Benzel, I., Barde, Y.A., Casademunt, E. Gene (2001) [Pubmed]
  32. c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. Palmada, M., Kanwal, S., Rutkoski, N.J., Gustafson-Brown, C., Johnson, R.S., Wisdom, R., Carter, B.D., Gufstafson-Brown, C. J. Cell Biol. (2002) [Pubmed]
  33. Notch and NGF/p75NTR control dendrite morphology and the balance of excitatory/inhibitory synaptic input to hippocampal neurones through Neurogenin 3. Salama-Cohen, P., Arévalo, M.A., Grantyn, R., Rodríguez-Tébar, A. J. Neurochem. (2006) [Pubmed]
  34. P75 neurotrophin receptor regulates expression of neural cell adhesion molecule 1. Mirnics, Z.K., Yan, C., Portugal, C., Kim, T.W., Saragovi, H.U., Sisodia, S.S., Mirnics, K., Schor, N.F. Neurobiol. Dis. (2005) [Pubmed]
  35. Differential effects of endogenous brain-derived neurotrophic factor on the survival of axotomized sensory neurons in dorsal root ganglia: a possible role for the p75 neurotrophin receptor. Zhou, X.F., Li, W.P., Zhou, F.H., Zhong, J.H., Mi, J.X., Wu, L.L., Xian, C.J. Neuroscience (2005) [Pubmed]
  36. TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal. Majdan, M., Walsh, G.S., Aloyz, R., Miller, F.D. J. Cell Biol. (2001) [Pubmed]
  37. Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning. Carter, A.R., Berry, E.M., Segal, R.A. Mol. Cell. Neurosci. (2003) [Pubmed]
  38. The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. Bamji, S.X., Majdan, M., Pozniak, C.D., Belliveau, D.J., Aloyz, R., Kohn, J., Causing, C.G., Miller, F.D. J. Cell Biol. (1998) [Pubmed]
  39. Neurotrophin receptor interacting factor (NRIF) is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor. Linggi, M.S., Burke, T.L., Williams, B.B., Harrington, A., Kraemer, R., Hempstead, B.L., Yoon, S.O., Carter, B.D. J. Biol. Chem. (2005) [Pubmed]
  40. A role for p75 neurotrophin receptor in the control of apoptosis-driven hair follicle regression. Botchkarev, V.A., Botchkareva, N.V., Albers, K.M., Chen, L.H., Welker, P., Paus, R. FASEB J. (2000) [Pubmed]
  41. Regulation, cellular localization, and function of the p75 neurotrophin receptor (p75NTR) during the regeneration of facial motoneurons. Gschwendtner, A., Liu, Z., Hucho, T., Bohatschek, M., Kalla, R., Dechant, G., Raivich, G. Mol. Cell. Neurosci. (2003) [Pubmed]
  42. Anterograde axonal transport of BDNF and NT-3 by retinal ganglion cells: roles of neurotrophin receptors. Butowt, R., von Bartheld, C.S. Mol. Cell. Neurosci. (2005) [Pubmed]
  43. Rescue of dorsal root sensory neurons by nerve growth factor and neurotrophin-3, but not brain-derived neurotrophic factor or neurotrophin-4, is dependent on the level of the p75 neurotrophin receptor. Barrett, G.L., Georgiou, A., Reid, K., Bartlett, P.F., Leung, D. Neuroscience (1998) [Pubmed]
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