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Gene Review

CNTFR  -  ciliary neurotrophic factor receptor

Homo sapiens

Synonyms: CNTF receptor subunit alpha, CNTFR-alpha, Ciliary neurotrophic factor receptor subunit alpha
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Disease relevance of CNTFR


Psychiatry related information on CNTFR


High impact information on CNTFR


Biological context of CNTFR


Anatomical context of CNTFR

  • The specificity conferring alpha subunit of the CNTF complex (CNTFR alpha), is extremely well conserved across species, and has a distribution localized predominantly to the nervous system and skeletal muscle [13].
  • CNTFR alpha lacks a conventional transmembrane domain and is thought to be anchored to the cell membrane by a glycosyl-phosphatidylinositol linkage [13].
  • The CNTFR gene was mapped to chromosome 9 by PCR on a panel of human/CHO somatic cell hybrids and localized to 9p13 by PCR on a panel of radiation hybrids [14].
  • We report that in the spinal cord of ALS patients there is a marked increase in the hybridisation signal for CNTFR alpha subunit mRNA overlying motor neurones [3].
  • In contrast, very little mRNA for CNTFR alpha subunit was found in the motor cortex and no differences were seen between ALS and controls [3].

Associations of CNTFR with chemical compounds

  • In contrast with the receptors for other known neurotrophic factors, which belong to the family of receptor tyrosine kinases, the CNTF receptor belongs to the family of cytokine receptors [15].
  • The developmental increase in atrial CNTF receptor mRNA was enhanced by stimulating muscarinic receptors with carbachol in ovo and was inhibited by blocking muscarinic cholinergic receptors with atropine [16].
  • Suppression of PGE2 and IL-8 synthesis was significantly greater (up to 42.6%, P < 0.05) by adding a 10-fold molar excess of soluble CNTF receptor (sCNTFR alpha) [17].
  • In addition, levels of mRNA for both the CNTF receptor alpha and gp130 subunits increased twofold as measured by RNase protection after treatment with retinoic acid for 30 h [18].

Physical interactions of CNTFR


Regulatory relationships of CNTFR

  • Human CNTF is a neurocytokine that elicits potent neurotrophic effects by activating a receptor complex composed of the ligand-specific alpha-receptor subunit (CNTFR alpha) and two signal transducing proteins, which together constitute a receptor for leukemia inhibitory factor (LIFR) [20].

Other interactions of CNTFR

  • As a result of this phenomenon, which can be rationalized in terms of the multivalent nature of CNTF receptor interaction, CNTF variants display striking changes in receptor selectivity [21].
  • Biological activities of the protein preparations were determined by their ability to induce proliferation of BAF/3 cells that were stably transfected with CNTF-R, gp130 and LIF-R cDNAs [22].
  • An NMR chemical shift perturbation study of the interaction between the BC domains of CNTFR and gp130 further mapped the interaction surface [5].
  • Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient [23].
  • Functionally active fusion protein of the novel composite cytokine CLC/soluble CNTF receptor [24].

Analytical, diagnostic and therapeutic context of CNTFR


  1. The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine. Plun-Favreau, H., Elson, G., Chabbert, M., Froger, J., deLapeyrière, O., Lelièvre, E., Guillet, C., Hermann, J., Gauchat, J.F., Gascan, H., Chevalier, S. EMBO J. (2001) [Pubmed]
  2. Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic shock: action mechanisms and role of CNTF receptor alpha. Demitri, M.T., Benigni, F., Meazza, C., Zinetti, M., Fratelli, M., Villa, P., Acheson, A., Panayotatos, N., Ghezzi, P. J. Inflamm. (1998) [Pubmed]
  3. Ciliary neurotrophic factor receptor expression in spinal cord and motor cortex in amyotrophic lateral sclerosis. Duberley, R.M., Johnson, I.P., Anand, P., Swash, M., Martin, J., Leigh, P.N., Zeman, S. J. Neurol. Sci. (1995) [Pubmed]
  4. A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes. Devergne, O., Hummel, M., Koeppen, H., Le Beau, M.M., Nathanson, E.C., Kieff, E., Birkenbach, M. J. Virol. (1996) [Pubmed]
  5. Solution structure of the C-terminal domain of the ciliary neurotrophic factor (CNTF) receptor and ligand free associations among components of the CNTF receptor complex. Man, D., He, W., Sze, K.H., Gong, K., Smith, D.K., Zhu, G., Ip, N.Y. J. Biol. Chem. (2003) [Pubmed]
  6. Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth. DeChiara, T.M., Vejsada, R., Poueymirou, W.T., Acheson, A., Suri, C., Conover, J.C., Friedman, B., McClain, J., Pan, L., Stahl, N., Ip, N.Y., Yancopoulos, G.D. Cell (1995) [Pubmed]
  7. LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Davis, S., Aldrich, T.H., Stahl, N., Pan, L., Taga, T., Kishimoto, T., Ip, N.Y., Yancopoulos, G.D. Science (1993) [Pubmed]
  8. Released form of CNTF receptor alpha component as a soluble mediator of CNTF responses. Davis, S., Aldrich, T.H., Ip, N.Y., Stahl, N., Scherer, S., Farruggella, T., DiStefano, P.S., Curtis, R., Panayotatos, N., Gascan, H. Science (1993) [Pubmed]
  9. The receptor for ciliary neurotrophic factor. Davis, S., Aldrich, T.H., Valenzuela, D.M., Wong, V.V., Furth, M.E., Squinto, S.P., Yancopoulos, G.D. Science (1991) [Pubmed]
  10. Genomic organization and chromosomal localization of the human and mouse genes encoding the alpha receptor component for ciliary neurotrophic factor. Valenzuela, D.M., Rojas, E., Le Beau, M.M., Espinosa, R., Brannan, C.I., McClain, J., Masiakowski, P., Ip, N.Y., Copeland, N.G., Jenkins, N.A. Genomics (1995) [Pubmed]
  11. Identification of ciliary neurotrophic factor (CNTF) residues essential for leukemia inhibitory factor receptor binding and generation of CNTF receptor antagonists. Di Marco, A., Gloaguen, I., Graziani, R., Paonessa, G., Saggio, I., Hudson, K.R., Laufer, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  12. C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women. Roth, S.M., Metter, E.J., Lee, M.R., Hurley, B.F., Ferrell, R.E. J. Appl. Physiol. (2003) [Pubmed]
  13. The ciliary neurotrophic factor and its receptor, CNTFR alpha. Sleeman, M.W., Anderson, K.D., Lambert, P.D., Yancopoulos, G.D., Wiegand, S.J. Pharmaceutica acta Helvetiae. (2000) [Pubmed]
  14. Localization of the gene for the ciliary neurotrophic factor receptor (CNTFR) to human chromosome 9. Donaldson, D.H., Britt, D.E., Jones, C., Jackson, C.L., Patterson, D. Genomics (1993) [Pubmed]
  15. The molecular biology of the CNTF receptor. Davis, S., Yancopoulos, G.D. Curr. Opin. Cell Biol. (1993) [Pubmed]
  16. Reciprocal regulation of ciliary neurotrophic factor receptors and acetylcholine receptors during synaptogenesis in embryonic chick atria. Wang, X., Halvorsen, S.W. J. Neurosci. (1998) [Pubmed]
  17. Ciliary neurotrophic factor combined with soluble receptor inhibits synthesis of proinflammatory cytokines and prostaglandin-E2 in vitro. Shapiro, L., Panayotatos, N., Meydani, S.N., Wu, D., Dinarello, C.A. Exp. Cell Res. (1994) [Pubmed]
  18. Opposing regulation of ciliary neurotrophic factor receptors on neuroblastoma cells by distinct differentiating agents. Malek, R.L., Halvorsen, S.W. J. Neurobiol. (1997) [Pubmed]
  19. The tails of two proteins: the scrapie prion protein and the ciliary neurotrophic factor receptor. Stahl, N., Boulton, T.G., Ip, N., Davis, S., Yancopoulos, G.D. Braz. J. Med. Biol. Res. (1994) [Pubmed]
  20. CNTF variants with increased biological potency and receptor selectivity define a functional site of receptor interaction. Saggio, I., Gloaguen, I., Poiana, G., Laufer, R. EMBO J. (1995) [Pubmed]
  21. Agonistic and antagonistic variants of ciliary neurotrophic factor (CNTF) reveal functional differences between membrane-bound and soluble CNTF alpha-receptor. Di Marco, A., Gloaguen, I., Demartis, A., Saggio, I., Graziani, R., Paonessa, G., Laufer, R. J. Biol. Chem. (1997) [Pubmed]
  22. Human ciliary neurotrophic factor: a structure-function analysis. Krüttgen, A., Grötzinger, J., Kurapkat, G., Weis, J., Simon, R., Thier, M., Schröder, M., Heinrich, P., Wollmer, A., Comeau, M. Biochem. J. (1995) [Pubmed]
  23. Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient. Rousseau, F., Gauchat, J.F., McLeod, J.G., Chevalier, S., Guillet, C., Guilhot, F., Cognet, I., Froger, J., Hahn, A.F., Knappskog, P.M., Gascan, H., Boman, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  24. Functionally active fusion protein of the novel composite cytokine CLC/soluble CNTF receptor. Guillet, C., Lelièvre, E., Plun-Favreau, H., Froger, J., Chabbert, M., Hermann, J., Benoit de Coignac, A., Bonnefoy, J.Y., Gascan, H., Gauchat, J.F., Elson, G. Eur. J. Biochem. (2002) [Pubmed]
  25. Expression of functional ciliary neurotrophic factor receptors in immortalized gonadotrophin-releasing hormone-secreting neurones. Dozio, E., Watanobe, H., Ruscica, M., Maggi, R., Motta, M., Magni, P. J. Neuroendocrinol. (2005) [Pubmed]
  26. CNTF and its receptor subunits in human gliomas. Weis, J., Schönrock, L.M., Züchner, S.L., Lie, D.C., Sure, U., Schul, C., Stögbauer, F., Ringelstein, E.B., Halfter, H. J. Neurooncol. (1999) [Pubmed]
  27. Novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) stimulates corticotroph function via a signal transducer and activator of transcription-dependent mechanism negatively regulated by suppressor of cytokine signaling-3. Auernhammer, C.J., Isele, N.B., Kopp, F.B., Spoettl, G., Cengic, N., Weber, M.M., Senaldi, G., Engelhardt, D. Endocrinology (2003) [Pubmed]
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