CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex

Nat Neurosci. 2000 Sep;3(9):867-72. doi: 10.1038/78765.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Differentiation / physiology
  • Cell Survival / physiology
  • Cytokines / metabolism*
  • Ligands
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Nerve Degeneration / physiopathology
  • Radioligand Assay
  • Receptor, Ciliary Neurotrophic Factor / metabolism*
  • Receptors, Cytokine / metabolism*
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • Ligands
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Cytokine
  • cardiotrophin-like cytokine
  • cytokine-like factor-1