Genomes and Genes
ciliary neurotrophic factor receptor
Summary: Cell surface receptors for CILIARY NEUROTROPHIC FACTOR. They are heterotrimeric proteins formed by the association of the CILIARY NEUROTROPHIC FACTOR RECEPTOR ALPHA SUBUNIT with the LEUKEMIA INHIBITORY FACTOR RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR GP130. Although the receptor regulates neuronal development, it is structurally similar to the cytokine receptor for INTERLEUKIN-6; (RECEPTORS, INTERLEUKIN-6).
- Buk D, Waibel M, Braig C, Martens A, Heinrich P, Graeve L. Polarity and lipid raft association of the components of the ciliary neurotrophic factor receptor complex in Madin-Darby canine kidney cells. J Cell Sci. 2004;117:2063-75 pubmed..CNTF-, LIF-, and IL-6-dependent STAT3 activation was sensitive to the cholesterol-depleting drug methyl-beta-cyclodextrin (MCD) suggesting that the integrity of lipid rafts is important for IL-6-type cytokine-induced STAT activation. ..
- Derouet D, Rousseau F, Alfonsi F, Froger J, Hermann J, Barbier F, et al. Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor. Proc Natl Acad Sci U S A. 2004;101:4827-32 pubmed publisher..Thus, NP is a new ligand for CNTFRalpha, with important implications for murine nervous system development...
- Beltran W, Rohrer H, Aguirre G. Immunolocalization of ciliary neurotrophic factor receptor alpha (CNTFRalpha) in mammalian photoreceptor cells. Mol Vis. 2005;11:232-44 pubmed..The expression of CNTFRalpha by rods and cones in non-rodent species may suggest a direct mechanism of action if CNTF administration results in photoreceptor rescue. ..
- Plun Favreau H, Elson G, Chabbert M, Froger J, Delapeyriere O, Lelievre E, et al. The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine. EMBO J. 2001;20:1692-703 pubmed..Together, these observations demonstrate that CNTFR induces the secretion of CLC, as well as mediating the functional responses of CLC. ..
- Beltran W, Zhang Q, Kijas J, Gu D, Rohrer H, Jordan J, et al. Cloning, mapping, and retinal expression of the canine ciliary neurotrophic factor receptor alpha (CNTFRalpha). Invest Ophthalmol Vis Sci. 2003;44:3642-9 pubmed..This could open novel pathways for the treatment of retinal degeneration in animal models and humans. ..
- Young W, Smith S, Chang C. Induction of the intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFRalpha) gene by the TR4 orphan receptor. A member of steroid receptor superfamily. J Biol Chem. 1997;272:3109-16 pubmed..5'-AGGTCAGAGGTCAGG-3'), has been identified in the 5th intron of the alpha component of the ciliary neurotrophic factor receptor (CNTFRalpha) gene for the human TR4 orphan receptor (TR4)...
- Rousseau F, Gauchat J, McLeod J, Chevalier S, Guillet C, Guilhot F, et al. Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient. Proc Natl Acad Sci U S A. 2006;103:10068-73 pubmed..Structural and docking interaction studies showed that the R197L substitution destabilized the contact site between CLC and CNTFRalpha. ..
- Garner A, Menegay H, Boeshore K, Xie X, Voci J, Johnson J, et al. Expression of TrkB receptor isoforms in the developing avian visual system. J Neurosci. 1996;16:1740-52 pubmed..Because BDNF is expressed in both the retina and tectum, it is conceivable that TrkB also mediates autocrine/paracrine signaling within these structures or anterograde retinotectal trophic support. ..
- Kokoeva M, Yin H, Flier J. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science. 2005;310:679-83 pubmed..These findings link the sustained effect of CNTF on energy balance to hypothalamic neurogenesis and suggest that regulated hypothalamic neurogenesis in adult mice may play a previously unappreciated role in physiology and disease. ..
- Ito Y, Yamamoto M, Mitsuma N, Li M, Hattori N, Sobue G. Expression of mRNAs for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors (CNTFR alpha, LIFR beta, IL-6R alpha, and gp130) in human peripheral neuropathies. Neurochem Res. 2001;26:51-8 pubmed
- Raju S, Zheng M, Schuleri K, Phan A, Bedja D, Saraiva R, et al. Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity. Proc Natl Acad Sci U S A. 2006;103:4222-7 pubmed
- Haniu M, Montestruque S, Bures E, Talvenheimo J, Toso R, Lewis Sandy S, et al. Interactions between brain-derived neurotrophic factor and the TRKB receptor. Identification of two ligand binding domains in soluble TRKB by affinity separation and chemical cross-linking. J Biol Chem. 1997;272:25296-303 pubmed..These results, obtained from a variety of experimental techniques, highlight the importance of two distinct regions of the extracellular domain of the TRKB receptor in binding BDNF. ..
- Slaugenhaupt S, Blumenfeld A, Liebert C, Mull J, Lucente D, Monahan M, et al. The human gene for neurotrophic tyrosine kinase receptor type 2 (NTRK2) is located on chromosome 9 but is not the familial dysautonomia gene. Genomics. 1995;25:730-2 pubmed..The NTRK2 gene is located approximately 22 cm proximal to DYS and shows several recombinants in disease families. Therefore, the NTRK2 gene can now be excluded as a candidate gene for familial dysautonomia. ..
- Iwasaki Y, Gay B, Wada K, Koizumi S. Association of the Src family tyrosine kinase Fyn with TrkB. J Neurochem. 1998;71:106-11 pubmed..All these data suggest the involvement of Fyn in the neurotrophin signal transduction pathways downstream of TrkB. ..
- Yamasaki Y, Shigeno T, Furukawa Y, Furukawa S. Reduction in brain-derived neurotrophic factor protein level in the hippocampal CA1 dendritic field precedes the delayed neuronal damage in the rat brain. J Neurosci Res. 1998;53:318-29 pubmed..Thus, a dysfunctional autocrine mechanism of BDNF within the CA1 neuron may be involved in the pathogenesis of selective neuronal damage after ischemia. ..
- Robert P, Peterson A, Eyer J. Neurofilament cytoskeleton disruption does not modify accumulation of trophic factor mRNA. J Neurosci Res. 2001;64:487-92 pubmed..Consistently with the prolonged survival of neurons expressing atypical or abnormally distributed neurofilaments, no obvious changes were observed for any of the mRNA species examined. ..
- Park J, Howell M, Winseck A, Forger N. Effects of testosterone on the development of a sexually dimorphic neuromuscular system in ciliary neurotrophic factor receptor knockout mice. J Neurobiol. 1999;41:317-25 pubmed..Prenatal TP treatment of CNTFRalpha -/- males overcomes the effects of the gene deletion on the BC and LA muscles without a concomitant effect on SNB motoneuron number. ..
- Takamiya A, Takeda M, Yoshida A, Kiyama H. Inflammation induces serine protease inhibitor 3 expression in the rat pineal gland. Neuroscience. 2002;113:387-94 pubmed..In addition, the expression of ciliary neurotrophic factor receptor (CNTFR) and leukemia inhibitory factor receptor (LIFR) mRNAs, but not of interleukin 6 receptor ..
- Schulz Key S, Hofmann H, Beisenherz Huss C, Barbisch C, Kirsch M. Ciliary neurotrophic factor as a transient negative regulator of rod development in rat retina. Invest Ophthalmol Vis Sci. 2002;43:3099-108 pubmed
- Chalazonitis A, Rothman T, Chen J, Vinson E, MacLennan A, Gershon M. Promotion of the development of enteric neurons and glia by neuropoietic cytokines: interactions with neurotrophin-3. Dev Biol. 1998;198:343-65 pubmed..These observations support the idea that a ligand for the tripartite CNTF receptor complex plays a role in ENS development. ..
- Oakley R, Lefcort F, Clary D, Reichardt L, Prevette D, Oppenheim R, et al. Neurotrophin-3 promotes the differentiation of muscle spindle afferents in the absence of peripheral targets. J Neurosci. 1997;17:4262-74 pubmed..Together, our results indicate that NT3 signaling is both necessary and sufficient for the development of the proprioceptive phenotype, even in the absence of other signals from limb muscle. ..
- Guiton M, Gunn Moore F, Glass D, Geis D, Yancopoulos G, Tavare J. Naturally occurring tyrosine kinase inserts block high affinity binding of phospholipase C gamma and Shc to TrkC and neurotrophin-3 signaling. J Biol Chem. 1995;270:20384-90 pubmed
- Tripathi R, McTigue D. Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2 expression after spinal contusion in rats. J Comp Neurol. 2008;510:129-44 pubmed publisher..Thus, both CNTF and FGF-2 are present in regions of elevated OPC proliferation and oligodendrocyte generation after SCI and therefore may play a role in injury-induced gliogenesis. ..
- Hafidi A, Decourt B, MacLennan A. CNTFRalpha and CNTF expressions in the auditory brainstem: light and electron microscopy study. Hear Res. 2004;194:14-24 pubmed..The clear presence of CNTFRalpha at post-synaptic terminals and that of its ligand the CNTF in axons and puncta surrounding neuronal cell bodies suggest an anterograde mode of action for CNTF in the central auditory system. ..
- Lucini C, Castaldo L, Lamanna C, Maruccio L, Vega J, Gargiulo G. Neuronal and non-neuronal Trk neurotrophin receptor-like proteins in Eisenia foetida (Annelida Oligochaeta). Neurosci Lett. 1999;261:163-6 pubmed..TrkB- and TrkC-like immunoreactivity was observed in the gut innervation. Non-neuronal expression of TrkB and TrkC proteins was found in epidermal cells, and TrkC-like immunoreactivity was detected in the gut epithelium. ..
- Valter K, Bisti S, Stone J. Location of CNTFRalpha on outer segments: evidence of the site of action of CNTF in rat retina. Brain Res. 2003;985:169-75 pubmed
- Silos Santiago I, Fagan A, Garber M, Fritzsch B, Barbacid M. Severe sensory deficits but normal CNS development in newborn mice lacking TrkB and TrkC tyrosine protein kinase receptors. Eur J Neurosci. 1997;9:2045-56 pubmed
- Schimmang T, Alvarez Bolado G, Minichiello L, Vazquez E, Giraldez F, Klein R, et al. Survival of inner ear sensory neurons in trk mutant mice. Mech Dev. 1997;64:77-85 pubmed
- Coffey E, Akerman K, Courtney M. Brain derived neurotrophic factor induces a rapid upregulation of synaptophysin and tau proteins via the neurotrophin receptor TrkB in rat cerebellar granule cells. Neurosci Lett. 1997;227:177-80 pubmed..We conclude that BDNF, characterized to be survival promoting early in differentiation of cerebellar granule cells, enhances maturation at a later stage. ..
- Elmer E, Kokaia M, Ernfors P, Ferencz I, Kokaia Z, Lindvall O. Suppressed kindling epileptogenesis and perturbed BDNF and TrkB gene regulation in NT-3 mutant mice. Exp Neurol. 1997;145:93-103 pubmed..These results indicate that endogenous NT-3 levels can influence the rate of epileptogenesis, and suggest a link between NT-3 and BDNF gene regulation in dentate granule cells. ..
- Monroe R, Halvorsen S. Cadmium blocks receptor-mediated Jak/STAT signaling in neurons by oxidative stress. Free Radic Biol Med. 2006;41:493-502 pubmed
- Ip N, Stitt T, Tapley P, Klein R, Glass D, Fandl J, et al. Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells. Neuron. 1993;10:137-49 pubmed..However, we find that a neuronal environment does restrict the Trks in their ability to respond to their "nonpreferred" neurotrophin ligands. ..
- Cognet I, Guilhot F, Chevalier S, Guay Giroux A, Bert A, Elson G, et al. Expression of biologically active mouse ciliary neutrophic factor (CNTF) and soluble CNTFRalpha in Escherichia coli and characterization of their functional specificities. Eur Cytokine Netw. 2004;15:255-62 pubmed..It appears well suited for the comparative evaluation of CNTF and the two additional recently discovered CNTFR ligands, cardiotrophin-like cytokine\cytokine-like factor-1 and neuropoietin. ..
- Johann V, Jeliaznik N, Schrage K, Mey J. Retinoic acid downregulates the expression of ciliary neurotrophic factor in rat Schwann cells. Neurosci Lett. 2003;339:13-6 pubmed..In addition to CNTF, the mRNAs of leukemia inhibitory factor, interleukin-6, ciliary neurotrophic factor receptor component alpha and gp130 were detected in the Schwann cells.
- Armanini M, McMahon S, Sutherland J, Shelton D, Phillips H. Truncated and catalytic isoforms of trkB are co-expressed in neurons of rat and mouse CNS. Eur J Neurosci. 1995;7:1403-9 pubmed..In developing spinal cord ventral horn, an age-related increase in hybridization was observed for truncated isoforms. These findings suggest that truncated trkB may modulate neuronal responses to neurotrophins which act via trkB. ..
- Cherel M, Sorel M, Lebeau B, Dubois S, Moreau J, Bataille R, et al. Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11. Blood. 1995;86:2534-40 pubmed
- Bosco A, Linden R. BDNF and NT-4 differentially modulate neurite outgrowth in developing retinal ganglion cells. J Neurosci Res. 1999;57:759-69 pubmed..Moreover, highly homologous neurotrophins such as BDNF and NT-4, presumably activating via TrkB receptors, selectively control the differentiation of distinct ganglion cell neuritic morphologies. ..
- Dittrich F, Feng Y, Metzdorf R, Gahr M. Estrogen-inducible, sex-specific expression of brain-derived neurotrophic factor mRNA in a forebrain song control nucleus of the juvenile zebra finch. Proc Natl Acad Sci U S A. 1999;96:8241-6 pubmed..The up-regulation of the BDNF expression in the HVc could be a mechanism by which estrogen triggers the differentiation of cells within and connected to the HVc of male zebra finches. ..
- Mu X, Young W, Liu Y, Uemura H, Chang C. Induction of an intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFRalpha) gene by the TR3 orphan receptor. Endocrine. 1998;9:27-32 pubmed..CNTFRalpha-NBRE (5'-AAAGGTCA-3') has been identified in the fifth intron of the alpha component of ciliary neurotrophic factor receptor gene (CNTFR-15) for the human TR3 orphan receptor (TR3)...
- Hicks R, Zhang L, Dhillon H, Prasad M, Seroogy K. Expression of trkB mRNA is altered in rat hippocampus after experimental brain trauma. Brain Res Mol Brain Res. 1998;59:264-8 pubmed..These data demonstrate that lateral fluid-percussion injury modulates expression of trkB mRNA in the hippocampus and support a role for BDNF/trkB signalling mechanisms in secondary events associated with traumatic brain injury. ..
- Hackett S, Friedman Z, Freund J, Schoenfeld C, Curtis R, DiStefano P, et al. A splice variant of trkB and brain-derived neurotrophic factor are co-expressed in retinal pigmented epithelial cells and promote differentiated characteristics. Brain Res. 1998;789:201-12 pubmed..Signaling through trkB could play a role in differentiation of RPE cells during development and maintenance of the differentiated state in adult RPE. ..
- Man D, Xia Y, Sze K, Smith D, He W, Ip N, et al. Complete 1H, 15N and 13C assignments of the carboxyl terminal domain of the ciliary neurotrophic factor receptor (CNTFR). J Biomol NMR. 2002;22:95-6 pubmed
- Nakagawara A, Liu X, Ikegaki N, White P, Yamashiro D, Nycum L, et al. Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). Genomics. 1995;25:538-46 pubmed..5-kb band encodes the full-length TRK-B mRNA and the 8.0-kb band encodes the truncated form of TRK-B mRNA. By fluorescence in situ hybridization and somatic cell hybrid mapping, the human TRK-B gene was localized to chromosome 9q22.1. ..
- Rudge J, Li Y, Pasnikowski E, Mattsson K, Pan L, Yancopoulos G, et al. Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes. Eur J Neurosci. 1994;6:693-705 pubmed..Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocyte. ..
- Yamamoto M, Sobue G, Yamamoto K, Terao S, Mitsuma T. Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75NGFR, trkA, trkB, and trkC) in the adult human peripheral nervous system and nonneural tissues. Neurochem Res. 1996;21:929-38 pubmed
- Arce V, Pollock R, Philippe J, Pennica D, Henderson C, Delapeyriere O. Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J Neurosci. 1998;18:1440-8 pubmed..The possibility that they act together on individual motoneurons suggests that the motoneuron must integrate distinct signals from different cellular partners when deciding whether to die or to survive. ..
- Rodríguez Rivera N, Molina Hernández A, Sánchez Cruz E, Escalante Alcalde D, Velasco I. Activated Notch1 is a stronger astrocytic stimulus than leukemia inhibitory factor for rat neural stem cells. Int J Dev Biol. 2009;53:947-53 pubmed publisher..These experiments show that cells stimulated with NICD differentiate more readily to astrocytes than LIF-treated NSC. ..
- Kokaia M, Ernfors P, Kokaia Z, Elmer E, Jaenisch R, Lindvall O. Suppressed epileptogenesis in BDNF mutant mice. Exp Neurol. 1995;133:215-24 pubmed..These results show that BDNF plays an important role in establishing hyperexcitability during epileptogenesis, probably by increasing efficacy in stimulated synapses. ..
- Zhang C, Brandemihl A, Lau D, Lawton A, Oakley B. BDNF is required for the normal development of taste neurons in vivo. Neuroreport. 1997;8:1013-7 pubmed..The foliate taste papillae of neonatal bdnf-/- mice had similar defects. We conclude that the normal development of taste neurons requires BDNF. ..
- Calza L, Giardino L, Aloe L. NGF content and expression in the rat pituitary gland and regulation by thyroid hormone. Brain Res Mol Brain Res. 1997;51:60-8 pubmed..These data indicate that pituitary NGF is selectively modulated by thyroid status of the animal, further supporting a close link between NGF and thyroid hormone. ..
- Perez Castro C, Carbia Nagashima A, Paez Pereda M, Goldberg V, Chervin A, Carrizo G, et al. Effects of the gp130 cytokines ciliary neurotropic factor (CNTF) and interleukin-11 on pituitary cells: CNTF receptors on human pituitary adenomas and stimulation of prolactin and GH secretion in normal rat anterior pituitary aggregate cultures. J Endocrinol. 2001;169:539-47 pubmed..These data show that IL-11 and CNTF may act as regulatory factors in anterior pituitary cells, in which the three-dimensional structure of the gland is of critical importance. ..
- Roth S, Metter E, Lee M, Hurley B, Ferrell R. C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women. J Appl Physiol (1985). 2003;95:1425-30 pubmedWe performed gene screening of the ciliary neurotrophic factor receptor (CNTFR) gene and genotyped three newly identified polymorphisms: C-1703T in the 5' promoter region, T1069A in intron 5, and C174T in exon 9...
- Schuster B, Kovaleva M, Sun Y, Regenhard P, Matthews V, Grötzinger J, et al. Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF. J Biol Chem. 2003;278:9528-35 pubmed..Engineering a CNTFR-specific human CNTF variant may therefore be a prerequisite to improving the safety profile of CNTF. ..