The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

RTN4R  -  reticulon 4 receptor

Homo sapiens

Synonyms: NGR, NOGOR, NgR, Nogo receptor, Nogo-66 receptor, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of RTN4R

  • Here, we demonstrate that human NgR expressed in human neuroblastoma cells is constitutively cleaved in a post-ER compartment to generate a lipid-raft associated C-terminal fragment that is present on the cell surface and a soluble N-terminal fragment that is released into the medium [1].
  • Nogo-66 and MAG may therefore modulate glioma growth and migration by acting through the NgR, a phenomenon that has potential therapeutic implications [2].
  • Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis [3].
  • Potentiation of outgrowth-promoting signals, together with antagonism of myelin proteins or their convergent receptor, NgR, and its second messenger pathways, may provide new opportunities in the rational design of treatments for acute brain injury and neurodegenerative disorders [4].
  • Phage that display a surface peptide with the NGR sequence motif home selectively to tumor vasculature in vivo [5].

Psychiatry related information on RTN4R


High impact information on RTN4R

  • The Nogo-66(1 40) antagonist peptide (NEP1 40) blocks Nogo-66 or CNS myelin inhibition of axonal outgrowth in vitro, demonstrating that NgR mediates a significant portion of axonal outgrowth inhibition by myelin [7].
  • LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex [8].
  • 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) [8].
  • 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 [9].
  • Thus we conclude that p75(NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target for promoting nerve regeneration [9].

Chemical compound and disease context of RTN4R

  • Here, we demonstrate that the NgR-related protein NgR homologue-1 is released from neuroblastoma cells as a full-length ectodomain (NgRH1-ecto) and an N-terminal fragment (NTF-NgRH1) containing the leucine-rich repeat region of the protein [10].

Biological context of RTN4R


Anatomical context of RTN4R

  • Furthermore, the N- and C-terminal fragments of NgR were detectable in human brain cortex and the N-terminal fragment was also present in human cerebrospinal fluid, demonstrating that NgR proteolysis occurs within the human nervous system [1].
  • The Nogo receptor (NgR) plays a central role in mediating growth-inhibitory activities of myelin-derived proteins, thereby severely limiting axonal regeneration after injury of the adult mammalian central nervous system (CNS) [11].
  • Two novel mammalian Nogo receptor homologs differentially expressed in the central and peripheral nervous systems [15].
  • Identification of a functional epitope of the Nogo receptor by a combinatorial approach using ribosome display [11].
  • In the human fetus Nogo-R was transcribed in the ventral horn of the spinal cord and in dorsal root ganglia [16].

Associations of RTN4R with chemical compounds

  • Binding of MAG to NgR-expressing cells is GPI dependent and sialic acid independent [17].
  • Disulfide structure of the leucine-rich repeat C-terminal cap and C-terminal stalk region of Nogo-66 receptor [18].
  • Tumor-specific DXR uptake was completely blocked when mice were coinjected with a 50-fold molar excess of the soluble NGR peptide [19].
  • These results suggest that the NGR motif has a strong propensity to form beta-turn in linear peptides and may explain the finding that GNGRG peptide can target TNF to tumors, albeit to a lower extent than CNGRC [20].
  • Such interactions appear to be mediated by a highly conserved domain that contains an asparagine-glycine-arginine (NGR) motif known to bind alpha5beta1 integrin with moderate affinity [21].

Physical interactions of RTN4R

  • By applying this method of "affinity fingerprinting" to the NgR ligand binding domain we were able to detect a distinct region important for binding to Nogo [11].
  • Conversely, NgR binds to MAG-expressing cells [17].
  • OMG encodes for an inhibitor of neurite outgrowth by the binding to the Nogo-66 receptor (RTN4R) [22].
  • Here, we identify LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) as a potent axonal inhibitor of oligodendrocyte differentiation and myelination that is regulated by nerve growth factor and its cognate receptor TrkA in a dose-dependent manner [23].

Regulatory relationships of RTN4R


Other interactions of RTN4R


Analytical, diagnostic and therapeutic context of RTN4R

  • One hundred and twenty unrelated Italian schizophrenic patients were screened for mutations in the RTN4R gene using denaturing high performance liquid chromatography (DHPLC) [28].
  • 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 [9].
  • We show by in situ hybridisation and by RT-PCR that NGRL mRNAs are predominantly expressed in the neurons of the embryonic and adult central and peripheral nervous systems, and that they together with NGR possess distinct and partially nonoverlapping expression patterns [15].
  • We performed in situ hybridization in human and mouse nervous tissues to map the cellular distribution of Nogo-R gene activity patterns in fetal and adult human spinal cord and sensory ganglia, adult human brain, and the nervous systems of developing and adult mice [16].
  • By coupling NGR peptides that target the angiogenic endothelial cell marker aminopeptidase N to the surface of DXR-loaded liposomes [NGR-SL(DXR)], we obtained tumor regression, pronounced destruction of the tumor vasculature, and prolonged survival of orthotopic neuroblastoma xenografts [29].


  1. Zinc metalloproteinase-mediated cleavage of the human Nogo-66 receptor. Walmsley, A.R., McCombie, G., Neumann, U., Marcellin, D., Hillenbrand, R., Mir, A.K., Frentzel, S. J. Cell. Sci. (2004) [Pubmed]
  2. Nogo-66 and myelin-associated glycoprotein (MAG) inhibit the adhesion and migration of Nogo-66 receptor expressing human glioma cells. Liao, H., Duka, T., Teng, F.Y., Sun, L., Bu, W.Y., Ahmed, S., Tang, B.L., Xiao, Z.C. J. Neurochem. (2004) [Pubmed]
  3. Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis. Satoh, J., Onoue, H., Arima, K., Yamamura, T. J. Neuropathol. Exp. Neurol. (2005) [Pubmed]
  4. Neuronal growth-promoting and inhibitory cues in neuroprotection and neuroregeneration. Skaper, S.D. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  5. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Pasqualini, R., Koivunen, E., Kain, R., Lahdenranta, J., Sakamoto, M., Stryhn, A., Ashmun, R.A., Shapiro, L.H., Arap, W., Ruoslahti, E. Cancer Res. (2000) [Pubmed]
  6. Expression pattern of NOGO and NgR genes during human development. Al Halabiah, H., Delezoide, A.L., Cardona, A., Moalic, J.M., Simonneau, M. Gene Expr. Patterns (2005) [Pubmed]
  7. Nogo-66 receptor antagonist peptide promotes axonal regeneration. GrandPré, T., Li, S., Strittmatter, S.M. Nature (2002) [Pubmed]
  8. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Mi, S., Lee, X., Shao, Z., Thill, G., Ji, B., Relton, J., Levesque, M., Allaire, N., Perrin, S., Sands, B., Crowell, T., Cate, R.L., McCoy, J.M., Pepinsky, R.B. Nat. Neurosci. (2004) [Pubmed]
  9. A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Wong, S.T., Henley, J.R., Kanning, K.C., Huang, K.H., Bothwell, M., Poo, M.M. Nat. Neurosci. (2002) [Pubmed]
  10. Ectodomain shedding of human Nogo-66 receptor homologue-1 by zinc metalloproteinases. Walmsley, A.R., Mir, A.K., Frentzel, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  11. Identification of a functional epitope of the Nogo receptor by a combinatorial approach using ribosome display. Schimmele, B., Plückthun, A. J. Mol. Biol. (2005) [Pubmed]
  12. No association between the genetic polymorphisms in the RTN4R gene and schizophrenia in the Chinese population. Meng, J., Shi, Y., Zhao, X., Guo, S., Wang, H., Zheng, Y., Tang, R., Feng, G., Gu, N., Liu, H., Zhu, S., He, L. Journal of neural transmission (Vienna, Austria : 1996) (2007) [Pubmed]
  13. Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition. He, X.L., Bazan, J.F., McDermott, G., Park, J.B., Wang, K., Tessier-Lavigne, M., He, Z., Garcia, K.C. Neuron (2003) [Pubmed]
  14. The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Dechant, G., Barde, Y.A. Nat. Neurosci. (2002) [Pubmed]
  15. Two novel mammalian Nogo receptor homologs differentially expressed in the central and peripheral nervous systems. Laurén, J., Airaksinen, M.S., Saarma, M., Timmusk, T. Mol. Cell. Neurosci. (2003) [Pubmed]
  16. Nogo-receptor gene activity: cellular localization and developmental regulation of mRNA in mice and humans. Josephson, A., Trifunovski, A., Widmer, H.R., Widenfalk, J., Olson, L., Spenger, C. J. Comp. Neurol. (2002) [Pubmed]
  17. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Domeniconi, M., Cao, Z., Spencer, T., Sivasankaran, R., Wang, K., Nikulina, E., Kimura, N., Cai, H., Deng, K., Gao, Y., He, Z., Filbin, M. Neuron (2002) [Pubmed]
  18. Disulfide structure of the leucine-rich repeat C-terminal cap and C-terminal stalk region of Nogo-66 receptor. Wen, D., Wildes, C.P., Silvian, L., Walus, L., Mi, S., Lee, D.H., Meier, W., Pepinsky, R.B. Biochemistry (2005) [Pubmed]
  19. Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. Pastorino, F., Brignole, C., Marimpietri, D., Cilli, M., Gambini, C., Ribatti, D., Longhi, R., Allen, T.M., Corti, A., Ponzoni, M. Cancer Res. (2003) [Pubmed]
  20. Structure-activity relationships of linear and cyclic peptides containing the NGR tumor-homing motif. Colombo, G., Curnis, F., De Mori, G.M., Gasparri, A., Longoni, C., Sacchi, A., Longhi, R., Corti, A. J. Biol. Chem. (2002) [Pubmed]
  21. Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry. Asokan, A., Hamra, J.B., Govindasamy, L., Agbandje-McKenna, M., Samulski, R.J. J. Virol. (2006) [Pubmed]
  22. Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation. Venturin, M., Moncini, S., Villa, V., Russo, S., Bonati, M.T., Larizza, L., Riva, P. Neurogenetics (2006) [Pubmed]
  23. NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination. Lee, X., Yang, Z., Shao, Z., Rosenberg, S.S., Levesque, M., Pepinsky, R.B., Qiu, M., Miller, R.H., Chan, J.R., Mi, S. J. Neurosci. (2007) [Pubmed]
  24. TROY and LINGO-1 expression in astrocytes and macrophages/microglia in multiple sclerosis lesions. Satoh, J., Tabunoki, H., Yamamura, T., Arima, K., Konno, H. Neuropathol. Appl. Neurobiol. (2007) [Pubmed]
  25. The nogo-nogo receptor pathway limits a spectrum of adult CNS axonal growth. Cafferty, W.B., Strittmatter, S.M. J. Neurosci. (2006) [Pubmed]
  26. Mutation in the leucine-rich repeat C-flanking region of platelet glycoprotein Ib beta impairs assembly of von Willebrand factor receptor. Tang, J., Stern-Nezer, S., Liu, P.C., Matyakhina, L., Riordan, M., Luban, N.L., Steinbach, P.J., Kaler, S.G. Thromb. Haemost. (2004) [Pubmed]
  27. LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease. Majercak, J., Ray, W.J., Espeseth, A., Simon, A., Shi, X.P., Wolffe, C., Getty, K., Marine, S., Stec, E., Ferrer, M., Strulovici, B., Bartz, S., Gates, A., Xu, M., Huang, Q., Ma, L., Shughrue, P., Burchard, J., Colussi, D., Pietrak, B., Kahana, J., Beher, D., Rosahl, T., Shearman, M., Hazuda, D., Sachs, A.B., Koblan, K.S., Seabrook, G.R., Stone, D.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  28. Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia. Sinibaldi, L., De Luca, A., Bellacchio, E., Conti, E., Pasini, A., Paloscia, C., Spalletta, G., Caltagirone, C., Pizzuti, A., Dallapiccola, B. Hum. Mutat. (2004) [Pubmed]
  29. Targeting Liposomal Chemotherapy via Both Tumor Cell-Specific and Tumor Vasculature-Specific Ligands Potentiates Therapeutic Efficacy. Pastorino, F., Brignole, C., Di Paolo, D., Nico, B., Pezzolo, A., Marimpietri, D., Pagnan, G., Piccardi, F., Cilli, M., Longhi, R., Ribatti, D., Corti, A., Allen, T.M., Ponzoni, M. Cancer Res. (2006) [Pubmed]
WikiGenes - Universities