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receptor complex consisting of a specific CNTF receptor subunit α (CNTFRα) linked to
receptor complex consisting of a specific CNTF receptor subunit α (CNTFRα) linked to
the cell membrane with a glycosyl-phosphatidylinositol linkage, and two
the cell membrane with a glycosyl-phosphatidylinositol linkage, and two
-
signal-transducing transmembrane subunits LIF receptor beta (LIFR)β and gp130.
+
signal-transducing transmembrane subunits LIF receptor beta (LIFRβ) and gp130.
-
Binding of a CNTF dimer to CNTFRα is the requirement
+
Binding of a CNTF dimer to CNTFRα is the first requirement to initiate the
 +
signal transduction, which ultimately results in the enhanced transcription
 +
of responsive genes.

Revision as of 06:42, 8 May 2014

This Sandbox is Reserved from 01/04/2014, through 30/06/2014 for use in the course "510042. Protein structure, function and folding" taught by Prof Adrian Goldman, Tommi Kajander, Taru Meri, Konstantin Kogan and Juho Kellosalo at the University of Helsinki. This reservation includes Sandbox Reserved 923 through Sandbox Reserved 947.
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Contents

Introduction

Ciliary neutrophic factor (CNTF) is a nerve growth factor belonging to the interleukin-6 family of neuropoietic cytokines. Other members of this family include leukemia inhibitory factor (LIF), IL-6, IL-11 and oncostatin M (Wang 2012).

CNTFs biological functions involve affecting the growth, differentiation, survival and repair of various types of neurons and glial cells in both the central and peripheral nervous systems (). It has been suggested that CNTF is not an absolute requirement for neural development, but in fact functions in response to neural injuries and stresses.

CNTF exerts its biological function by binding into a tripartite receptor complex consisting of a specific CNTF receptor subunit α (CNTFRα) linked to the cell membrane with a glycosyl-phosphatidylinositol linkage, and two signal-transducing transmembrane subunits LIF receptor beta (LIFRβ) and gp130. Binding of a CNTF dimer to CNTFRα is the first requirement to initiate the signal transduction, which ultimately results in the enhanced transcription of responsive genes.


Fig. 1 X-ray structure of a truncated form of hCNTF (2-187)

Structure

Overview

CNTF is a roughly 22.7 kDa protein consisting of a single polypeptide chain of 200 amino acid residues. Like with many other cytokines, the tertiary structure of CNTF consists of four anti-parallel α-helices (A-D), where helices A-B and C-D are connected by two cross-over loops and helices B-C by one short loop.

Disease

References

Cognet I, Guilhot F, Chevalier S, Guay-Giroux A, Bert A, Elson GCA, Gascan H and Gauchat J-F: Expression of biologically active mouse ciliary neurotrophic factor (CNTF) and soluble CNTFRα in Eschericia coli and characterization of their functional specificities. Eur Cytokine Netw 15: 255-262 (2004).

Li Y, Tao W, Luo L, Huang D, Kauper K, Stabila P, LaVail MM, Laties AM and Wen R: CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration. PLoS One 5: 1-7 (2010).

Li Y, Wen R, Banzon T, Maminishkis A and Miller SS: CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium. PLoS One 6: 1-7 (2011).

McDonald NQ, Panayotatos N and Hendrickson WA: Crystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing. EMBO J 14: 2689-2699 (1995).

Richardson PM: Ciliary neurotrophic factor: A review. Pharmac Ther 63: 187-198 (1994).

Sieving PA, Caruse RC, Tao W, Coleman HR, Thompson DJS, Fullmer KR and Bush RA: Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants. PNAS 103: 3896-3901 (2006).

Sleeman MW, Anderson KD, Lambert PD, Yancopoulos GD and Wiegand SJ: The ciliary neurotrophic factor and its receptor, CNTFRα. Pharm Acta Helv 74: 265-272 (2000).

Wen R, Song Y, Kjellstrom S, Tanikawa A, Liu Y, Li Y, Zhao L, Bush RA, Laties AM and Sieving PA: Regulation of rod phototransduction machinery by ciliary neurotrophic factor. J Neurosci 26: 13523-13530 (2006).

Wen R, Tao W, Li Y and Sieving PA: CNTF and retina. Prog Retin Eye Res 31: 136-151 (2012).

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