Ciliary Neurotrophic Factor May Activate Mature Astrocytes via Binding with the Leukemia Inhibitory Factor Receptor

Autor: Muriel Coulpier, Marc Peschanski, Patrick A. Dreyfus, Christelle Monville, Danielle Riche, Elena Cattaneo, Marcienne Tardy, C. Fages, Luciano Conti, Claudio De-Fraja
Přispěvatelé: Neuroplasticité et thérapeutique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Regeneron Pharmaceuticals Inc., Institute of Pharmacological Sciences, Partenaires INRAE
Rok vydání: 2001
Předmět:
medicine.medical_specialty
Leukemia Inhibitory Factor Receptor alpha Subunit
Receptors
OSM-LIF
MAP Kinase Signaling System
medicine.medical_treatment
Leukemia inhibitory factor receptor
Ciliary neurotrophic factor
stat
law.invention
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
In vivo
law
Internal medicine
Glial Fibrillary Acidic Protein
medicine
Animals
Ciliary Neurotrophic Factor
Receptors
Cytokine
Receptor
Receptor
Ciliary Neurotrophic Factor
Molecular Biology
030304 developmental biology
Mice
Knockout
Neurons
0303 health sciences
Dose-Response Relationship
Drug
biology
Antagonist
Cell Differentiation
Cell Biology
Cell biology
Endocrinology
Cytokine
Astrocytes
biology.protein
Recombinant DNA
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Dimerization
030217 neurology & neurosurgery
Signal Transduction
Zdroj: Molecular and Cellular Neuroscience
Molecular and Cellular Neuroscience, Elsevier, 2001, 17 (2), pp.373-384. ⟨10.1006/mcne.2000.0926⟩
ISSN: 1044-7431
1095-9327
Popis: International audience; Ciliary neurotrophic factor (CNTF) acts on immature astrocytes that express its trimeric receptor. In contrast, mature astrocytes do not significantly express the specific CNTFalpha receptor subunit, yet they respond to CNTF administration in vivo. Here we show that this controversy may be solved by a shift in astroglial sensitivity to CNTF over time, related to a change in the type of receptor bound by the cytokine on mature astrocytes. A convergent set of results supports the hypothesis that the CNTF effect is due to the illegitimate binding on the leukemia inhibitory factor receptor (LIFR): (i) it requires high concentration of recombinant rat CNTF; (ii) it involves the Jak/Stat and Ras-MAPK pathways; (iii) it is preserved in CNTFRalpha-/- cells; (iv) it is potentiated by soluble CNTFRalpha added to the medium; and (v) it is significantly decreased by a partial antagonist of LIFR. On these bases, we propose a mechanistic model in which, in the adult brain, a CNTF/LIFR interglial system may be modulated by neurons that synthesize CNTFRalpha.
Databáze: OpenAIRE
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