The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine

Ciliary neurotrophic factor (CNTF) is involved in the survival of a number of different neural cell types, including motor neurons. CNTF functional re sponses are mediated through a triparaite membrane receptor composed of two signalling receptor chains, gp130 and the leukaemia inhibitory factor rece ptor (LIFR), associated with a non-signalling CNTF binding receptor a compo nent (CNTFR). CNTFR-deficient mice show profound neuronal deficits at birth , leading to a lethal phenotype, In contrast, inactivation of the CNTF gene leads only to a slight muscle weakness, mainly during adulthood, suggestin g that CNTFR binds to a second ligand that is important for development. Mo delling studies of the interleukin-6 family member cardiotrophin-like cytok ine (CLC) revealed structural similarities with CNTF, including the conserv ation of a site I domain involved in binding to CNTFR, Coexpression of CEC and CNTFR in mammalian cells generates a secreted composite cytokine, displ aying activities on cells expressing the gp130-LIFR complex on their surfac e, Correspondingly, CLC-CNTPR activates gp130, LIFR and STAT3 signalling co mponents, and enhances motor neuron survival. Together, these observations demonstrate that CNTFR induces the secretion of CLC, as well as mediating t he functional responses of CLC.