CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex.
Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, CNTFR, and two signaling beta chains, gp130 and the 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 have identified this factor as a stable secreted complex of cardiotrophin-like cytokine (CLC) and the soluble receptor cytokine-like factor-1 (CLF). CLF expression was required for CLC secretion, and the complex acted only on cells expressing functional CNTF receptors. The CLF/CLC complex activated gp130, LIFR and signal transducer and activator of transcription 3 (STAT3) and supported motor neuron survival. Our results indicate that the CLF/CLC complex is a second ligand for CNTFR with potentially important implications in nervous system development.
Elson
G C
GC
Centre d'Immunologie Pierre Fabre, 5 Avenue Napoleon III, 74164 St. Julien-en-Genevois, France.
Lelièvre
E
E
Guillet
C
C
Chevalier
S
S
Plun-Favreau
H
H
Froger
J
J
Suard
I
I
de Coignac
A B
AB
Delneste
Y
Y
Bonnefoy
J Y
JY
Gauchat
J F
JF
Gascan
H
H
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D008024:Ligands; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009410:Nerve Degeneration / Q000503:physiopathology; D011869:Radioligand Assay; D020801:Receptor, Ciliary Neurotrophic Factor / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D008024:Ligands; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; C121169:cardiotrophin-like cytokine; C113554:cytokine-like factor-1