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Jorge Larrivasahd - One of the best experts on this subject based on the ideXlab platform.
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cytological organization of the Alpha Component of the anterior olfactory nucleus and olfactory limbus
Frontiers in Neuroanatomy, 2012Co-Authors: Jorge LarrivasahdAbstract:This study describes the microscopic organization of a wedge-shaped area at the intersection of the main (MOB) and accessory olfactory bulbs (AOBs), or olfactory limbus (OL), and an additional Component of the anterior olfactory nucleus or Alpha AON that lies underneath of the AOB. The OL consists of a modified bulbar cortex bounded anteriorly by the MOB and posteriorly by the AOB. In Nissl-stained specimens the OL differs from the MOB by a progressive, antero-posterior decrease in thickness or absence of the external plexiform, mitral/tufted cell, and granule cell layers. On cytoarchitectual grounds the OL is divided from rostral to caudal into three distinct Components: a stripe of glomerular-free cortex or preolfactory area (PA), a second or necklace glomerular area, and a wedge-shaped or interstitial area (INA) crowned by the so-called modified glomeruli that appear to belong to the anterior AOB. The strategic location and interactions with the main and AOBs, together with the previously noted functional and connectional evidence, suggest that the OL may be related to both sensory modalities. The Alpha Component of the anterior olfactory nucleus, a slender cellular cluster (i.e., 650 × 150 μm) paralleling the base of the AOB, contains two neuron types: a pyramidal-like neuron and an interneuron. Dendrites of pyramidal-like cells (P-L) organize into a single bundle that ascends avoiding the AOB to resolve in a trigone bounded by the edge of the OL, the AOB and the dorsal part of the anterior olfactory nucleus. Utrastructurally, the neuropil of the Alpha Component contains three types of synaptic terminals; one of them immunoreactive to the enzyme glutamate decarboxylase, isoform 67.
Catherine Guillet - One of the best experts on this subject based on the ideXlab platform.
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Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: François Rousseau, Sylvie Chevalier, Catherine Guillet, Josy Froger, Isabelle Cognet, Florence Guilhot, Jean-françois Gauchat, James G. Mcleod, Angelika F Hahn, Per M. KnappskogAbstract:Ciliary neurotrophic factor (CNTF) receptor controls a pathway supporting the differentiation and survival of a wide range of neural cell types during development and in adulthood. Cardiotrophin-like cytokine (CLC)-cytokine-like factor 1 (CLF) composite cytokine is a second ligand for the CNTF Alpha-Component receptor (CNTFRAlpha). This composite cytokine is built on the structural model of IL-12, with a complex formed by a four-helix bundle type I cytokine, CLC (also referred to as CLCF1), bound to a soluble receptor subunit, CLF (also known as CRLF1). We have reported mutations in the chaperone soluble receptor CLF, causing cold-induced sweating syndrome (CISS). In this study, we studied the CLC-mutated alleles in a patient suffering from a similar disease. This patient was compound heterozygous for two different CLC mutations. The first allele was inactivated by a stop codon at position 107 (Y107X). In the second allele, a R197L mutation in the CLC-predicted binding site to the CNTFRAlpha was detected. Functional analysis of the mutated protein revealed an incapacity for R197L CLC to bind to CNTFRAlpha and activate the subsequent signaling events. Structural and docking interaction studies showed that the R197L substitution destabilized the contact site between CLC and CNTFRAlpha.
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Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Damien Derouet, François Rousseau, Catherine Guillet, Caroline Diveu, Josy Froger, Fabien Barbier, Fabienne Alfonsi, Jacques Hermann, David Perret, Laurence PreisserAbstract:A structural profile-based computational screen was used to identify neuropoietin (NP), a new cytokine. The np gene is localized in tandem with the cardiotrophin-1 gene on mouse chromosome 7. NP shares structural and functional features with ciliary neurotrophic factor (CNTF), cardiotrophin-1, and cardiotrophin-like cytokine. It acts through a membrane receptor complex comprising CNTF receptor-Alpha Component (CNTFRAlpha), gp130, and leukemia inhibitory factor receptor to activate signal transducer and activator of transcription 3 signaling pathway. NP is highly expressed in embryonic neuroepithelia. Strikingly, CNTFRAlpha, but not its alternate ligands, CNTF and cardiotrophin-like cytokine, is expressed at the same developmental stages. NP is also observed in retina and to a lesser extent in skeletal muscle. Moreover, NP could sustain the in vitro survival of embryonic motor neurons and could increase the proliferation of neural precursors when associated to epidermal growth factor and fibroblast growth factor 2. Thus, NP is a new ligand for CNTFRAlpha, with important implications for murine nervous system development.
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signaling pathways recruited by the cardiotrophin like cytokine cytokine like factor 1 composite cytokine specific requirement of the membrane bound form of ciliary neurotrophic factor receptor Alpha Component
Journal of Biological Chemistry, 2001Co-Authors: Eric Lelièvre, Sylvie Chevalier, Catherine Guillet, Josy Froger, Greg Elson, Jean-françois Gauchat, Helene Plunfavreau, Hugues GascanAbstract:Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of a number of neural cell types. Its receptor complex consists of a ligand-binding Component, CNTF receptor (CNTFR), associated with two signaling receptor Components, gp130 and leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second developmentally important ligand. We recently demonstrated that cardiotrophin-like cytokine (CLC) associates with the soluble orphan receptor cytokine-like factor-1 (CLF) to form a heterodimeric cytokine that displayed activities only on cells expressing the tripartite CNTF receptor on their surface. In this present study we examined the membrane binding of the CLC/CLF composite cytokine and observed a preferential interaction of the cytokine with the CNTFR subunit. Signaling pathways recruited by the CLC/CLF complex in human neuroblastoma cell lines were also analyzed in detail. The results obtained showed an activation of Janus kinases (JAK1, JAK2, and TYK2) leading to a tyrosine phosphorylation of the gp130 and LIFR. The phosphorylated signaling receptors served in turn as docking proteins for signal transducing molecules such as STAT3 and SHP-2. In vitro analysis revealed that the gp130-LIFR pathway could also stimulate the phosphatidylinositol 3-kinase and the mitogen-activated protein kinase pathways. In contrast to that reported before for CNTF, soluble CNTFR failed to promote the action CLC/CLF, and an absolute requirement of the membrane form of CNTFR was required to generate a functional response to the composite cytokine. This study reinforces the functional similarity between CNTF and the CLC/CLF composite cytokine defining the second ligand for CNTFR.
Josy Froger - One of the best experts on this subject based on the ideXlab platform.
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Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: François Rousseau, Sylvie Chevalier, Catherine Guillet, Josy Froger, Isabelle Cognet, Florence Guilhot, Jean-françois Gauchat, James G. Mcleod, Angelika F Hahn, Per M. KnappskogAbstract:Ciliary neurotrophic factor (CNTF) receptor controls a pathway supporting the differentiation and survival of a wide range of neural cell types during development and in adulthood. Cardiotrophin-like cytokine (CLC)-cytokine-like factor 1 (CLF) composite cytokine is a second ligand for the CNTF Alpha-Component receptor (CNTFRAlpha). This composite cytokine is built on the structural model of IL-12, with a complex formed by a four-helix bundle type I cytokine, CLC (also referred to as CLCF1), bound to a soluble receptor subunit, CLF (also known as CRLF1). We have reported mutations in the chaperone soluble receptor CLF, causing cold-induced sweating syndrome (CISS). In this study, we studied the CLC-mutated alleles in a patient suffering from a similar disease. This patient was compound heterozygous for two different CLC mutations. The first allele was inactivated by a stop codon at position 107 (Y107X). In the second allele, a R197L mutation in the CLC-predicted binding site to the CNTFRAlpha was detected. Functional analysis of the mutated protein revealed an incapacity for R197L CLC to bind to CNTFRAlpha and activate the subsequent signaling events. Structural and docking interaction studies showed that the R197L substitution destabilized the contact site between CLC and CNTFRAlpha.
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Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Damien Derouet, François Rousseau, Catherine Guillet, Caroline Diveu, Josy Froger, Fabien Barbier, Fabienne Alfonsi, Jacques Hermann, David Perret, Laurence PreisserAbstract:A structural profile-based computational screen was used to identify neuropoietin (NP), a new cytokine. The np gene is localized in tandem with the cardiotrophin-1 gene on mouse chromosome 7. NP shares structural and functional features with ciliary neurotrophic factor (CNTF), cardiotrophin-1, and cardiotrophin-like cytokine. It acts through a membrane receptor complex comprising CNTF receptor-Alpha Component (CNTFRAlpha), gp130, and leukemia inhibitory factor receptor to activate signal transducer and activator of transcription 3 signaling pathway. NP is highly expressed in embryonic neuroepithelia. Strikingly, CNTFRAlpha, but not its alternate ligands, CNTF and cardiotrophin-like cytokine, is expressed at the same developmental stages. NP is also observed in retina and to a lesser extent in skeletal muscle. Moreover, NP could sustain the in vitro survival of embryonic motor neurons and could increase the proliferation of neural precursors when associated to epidermal growth factor and fibroblast growth factor 2. Thus, NP is a new ligand for CNTFRAlpha, with important implications for murine nervous system development.
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signaling pathways recruited by the cardiotrophin like cytokine cytokine like factor 1 composite cytokine specific requirement of the membrane bound form of ciliary neurotrophic factor receptor Alpha Component
Journal of Biological Chemistry, 2001Co-Authors: Eric Lelièvre, Sylvie Chevalier, Catherine Guillet, Josy Froger, Greg Elson, Jean-françois Gauchat, Helene Plunfavreau, Hugues GascanAbstract:Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of a number of neural cell types. Its receptor complex consists of a ligand-binding Component, CNTF receptor (CNTFR), associated with two signaling receptor Components, gp130 and leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second developmentally important ligand. We recently demonstrated that cardiotrophin-like cytokine (CLC) associates with the soluble orphan receptor cytokine-like factor-1 (CLF) to form a heterodimeric cytokine that displayed activities only on cells expressing the tripartite CNTF receptor on their surface. In this present study we examined the membrane binding of the CLC/CLF composite cytokine and observed a preferential interaction of the cytokine with the CNTFR subunit. Signaling pathways recruited by the CLC/CLF complex in human neuroblastoma cell lines were also analyzed in detail. The results obtained showed an activation of Janus kinases (JAK1, JAK2, and TYK2) leading to a tyrosine phosphorylation of the gp130 and LIFR. The phosphorylated signaling receptors served in turn as docking proteins for signal transducing molecules such as STAT3 and SHP-2. In vitro analysis revealed that the gp130-LIFR pathway could also stimulate the phosphatidylinositol 3-kinase and the mitogen-activated protein kinase pathways. In contrast to that reported before for CNTF, soluble CNTFR failed to promote the action CLC/CLF, and an absolute requirement of the membrane form of CNTFR was required to generate a functional response to the composite cytokine. This study reinforces the functional similarity between CNTF and the CLC/CLF composite cytokine defining the second ligand for CNTFR.
David E Levy - One of the best experts on this subject based on the ideXlab platform.
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two domains of isgf3 gamma that mediate protein dna and protein protein interactions during transcription factor assembly contribute to dna binding specificity
Molecular and Cellular Biology, 1993Co-Authors: Susan A Veals, Santa T Maria, David E LevyAbstract:Abstract Alpha interferon (IFN-Alpha) induces the transcription of a large set of genes through activation of multimeric transcription factor ISGF3. This factor can be dissociated into two protein Components, termed ISGF3 gamma and ISGF3 Alpha. ISGF3 gamma is a 48-kDa protein related at the amino terminus to members of the IFN-regulatory factor (IRF) and Myb families of DNA-binding proteins; ISGF3 Alpha consists of three polypeptides of 84, 91, and 113 kDa that self-assemble to form an activated Component in response to IFN-Alpha. DNA-binding studies indicated that ISGF3 gamma binds DNA alone, recognizing the IFN-stimulated response element, while the ISGF3 Alpha polypeptides alone display no specific interactions with DNA. A complex between ISGF3 gamma and activated ISGF3 Alpha binds the IFN-stimulated response element with much greater affinity than does the 48-kDa ISGF3 gamma protein alone. The DNA-binding domain of ISGF3 gamma and regions responsible for protein-protein interaction with ISGF3 Alpha were identified by using deleted forms of ISGF3 gamma expressed in vitro. The amino-terminal region of ISGF3 gamma homologous to the IRF and Myb proteins was sufficient for interaction with DNA and displayed the binding specificity of the intact protein; phosphorylation of this region was necessary for activity. A second region of 160 amino acids separated from the DNA-binding domain by over 100 amino acids contained a domain capable of associating with ISGF3 Alpha and was sufficient to confer specific ISGF3 Alpha interaction to a heterologous protein. Interaction of the ISGF3 Alpha Component with the protein interaction domain of ISGF3 gamma altered the DNA-binding specificity of the resulting complex, suggesting that one or more of the ISGF3 Alpha polypeptides make base-specific contacts with DNA. This interaction defines a mechanism through which IRF-like proteins complexed with regulatory Components can display novel DNA-binding specificities.
G.d. Yancopoulos - One of the best experts on this subject based on the ideXlab platform.
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Ciliary neurotrophic factor maintains the pluripotentiality of embryonic stem cells
Development (Cambridge England), 1993Co-Authors: Joanne C. Conover, W. T. Poueymirou, B. Bates, Mitchell Goldfarb, T. M. Dechiara, G.d. YancopoulosAbstract:Ciliary neurotrophic factor was discovered based on its ability to support the survival of ciliary neurons, and is now known to act on a variety of neuronal and glial populations. Two distant relatives of ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M, mimic ciliary neurotrophic factor with respect to its actions on cells of the nervous system. In contrast to ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M also display a broad array of actions on cells outside of the nervous system. The overlapping activities of leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor can be attributed to shared receptor Components. The specificity of ciliary neurotrophic factor for cells of the nervous system results from the restricted expression of the Alpha Component of the ciliary neurotrophic factor receptor complex, which is required to convert a functional leukemia inhibitory factor/oncostatin M receptor complex into a ciliary neurotrophic factor receptor complex. The recent observation that the Alpha Component of the ciliary neurotrophic factor receptor complex is expressed by very early neuronal precursors suggested that ciliary neurotrophic factor may act on even earlier precursors, particularly on cells previously thought to be targets for leukemia inhibitory factor action. Here we show the first example of ciliary neurotrophic factor responsiveness in cells residing outside of the nervous system by demonstrating that embryonic stem cells express a functional ciliary neurotrophic factor receptor complex, and that ciliary neurotrophic factor is similar to leukemia inhibitory factor in its ability to maintain the pluripotentiality of these cells.