The Receptor for Ciliary Neurotrophic Factor

Abstract

Although neurotrophic factors were originally isolated on the basis of their ability to support the survival of neurons, these molecules are now thought to influence many aspects of the development and maintenance of the nervous system. Identifying the receptors for these neurotrophic factors should aid in identifying the cells on which these factors act and in understanding their precise mechanisms of action. A "tagged-ligand panning" procedure was used to clone a receptor for ciliary neurotrophic factor (CNTF). This receptor is expressed exclusively within the nervous system and skeletal muscle. The CNTF receptor has a structure unrelated to the receptors utilized by the nerve growth factor family of neurotrophic molecules, but instead is most homologous to the receptor for a cytokine, interleukin-6. This similarity suggestes that the CNTF receptor, like the interleukin-6 receptor, requires a second, signal-transducing component. In contrast to all known receptors, the CNTF receptor is anchored to cell membranes by a glycosyl-phosphatidylinositol linkage.

Trophic Support of Motoneurons: Physiological, Pathophysiological, and Therapeutic Implications

“…The intracellular domain of the LIF binding unit shares sequence homology with gp130. Interestingly, in addition to its (low affinity) GPI-linked binding unit (17), CNTF needs not only gp130 but also the LIF low-affinity binding unit for signal transduction (5,42). Thus, LIF, interleukin-6, and oncostatin-M deserve a thorough evaluation as additional potential neurotrophic molecules for motoneurons.…”

Soluble receptors in human disease

“…The receptor for stem cell factor (c-kit) and the human growth hormone receptor use a combination of alternative mRNA splicing and proteolysis to generate soluble receptors; alternative splicing gives rise to membrane-bound receptors that are significantly more susceptible to proteolysis than their conventionally spliced counterparts [21,77]. Receptors that are associated with the membrane via a glycosyl-phosphotidyl inositol (GPI) linkage such as the ciliary neurotrophic factor (CNTF) receptor and the lipopolysaccharide (LPS) receptor (CD14) are also shed from the cell surface [60,61,82]. Although it was thought that cleavage of the GPI linkage was mediated by phospholipase C, analysis of the soluble LPS receptor cleavage site suggests that there may be other mechanisms of release [82].…”

“…1D). In this model, the soluble receptor binds ligand in the splicing IL-6R␣ [51][52][53][54][55][56] splicing, cleavage Ag gp130 [57][58][59] splicing I CNTFR [60,61] GPI Ag LIFR [62][63][64][65][66] splicing I Leptin R [67][68][69][70] splicing I IL-11R [71,72] splicing Ag, I IL-12 p40 [73][74][75][76] splicing Ag, I Stem cell factor R (c-kit) [77][78][79] combined I Interferon R [80][81] splicing Lipopolysaccharide R (CD14) [82][83][84][85] GPI I…”

Co-administration of Ciliary Neurotrophic Factor with Its Soluble Receptor Protects against Neuronal Death and Enhances Neurite Outgrowth

“…in response to injury (5)(6)(7). Fourth, although the expression of the specific receptor for CNTF, termed CNTFR␣, is normally restricted to the plasma membrane of neurons (8), surviving astrocytes in the penumbra of an injury also begin to express CNTFR␣ (9, 10) suggesting a mechanism by which the nervous system responds to sublethal environmental stress or injury.…”