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.

Ciliary neurotrophic factor may activate mature astrocytes via binding with the leukemia inhibitory factor receptor / C. Monville, M. Coulpier, L. Conti, C. De-Fraja, P. Dreyfus, C. Fages, D. Riche, M. Tardy, E. Cattaneo, M. Peschanski. - In: MOLECULAR AND CELLULAR NEUROSCIENCES. - ISSN 1044-7431. - 17:2(2001 Feb 02), pp. 373-384.

Ciliary neurotrophic factor may activate mature astrocytes via binding with the leukemia inhibitory factor receptor

L. Conti;E. Cattaneo;
2001-02-02

Abstract

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.
Animals ; Astrocytes ; Dose-Response Relationship, Drug ; Dimerization ; Cell Differentiation ; Glial Fibrillary Acidic Protein ; Mice ; Leukemia Inhibitory Factor Receptor alpha Subunit ; Mice, Knockout ; MAP Kinase Signaling System ; Receptors, Cytokine ; Ciliary Neurotrophic Factor ; Neurons ; Receptor, Ciliary Neurotrophic Factor ; Receptors, OSM-LIF ; Signal Transduction
Settore BIO/14 - Farmacologia
MOLECULAR AND CELLULAR NEUROSCIENCES
Article (author)
File in questo prodotto:
File Dimensione Formato  
12 Monville MCN 2001.pdf

non disponibili

436.18 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/206855
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 23
social impact