Ciliary neurotrophic factor structure

FIGURE 27-3 Neurotrophic cytokines and their receptors. Neurotrophic cytokines are related to IL6 and bind to cell surface receptor complexes that share a common structural organization. The four ligands interchangeably employ two distinct receptor subunits, leukemia inhibitory factor receptor 3 (LIF-Rpt) andgpl30, and some employ a ligand-specific a subunit. CNTF-R, ciliary neurotrophic factor CT-fR.cardiotrophin 1 receptor IL6-R, interleukin-6 receptor. 

Fig. 3. The gplSO family of cytokines and receptors. Schematic representation of gpl30 and leukemia inhibitory factor receptor (LIFR) oriented in a cell membrane. Of the four-helix bundle gplSO cytokines, structural information currently exists for human interleukin 6 (IL-6) (green) (Somers et al, 1997), human herpes virus interleukin 6 (HlTV-8 IL-6) (purple) (Chow et al, 2001a), ciliary neurotrophic factor (CNTF) (orange) (McDonald et al., 1995), leukemia inhibitory factor (LIF) (blue) (Robinson et al, 1994), and oncostatin-M (OSM) (red) (Deller et al, 2000). Lower panel is a detailed list of gplSO cytokines and the associated receptors incorporated into the final signaling complex. (See Color Insert.)...

McDonald, N. Q., Panayotatos, N., and Hendrickson, W. A. (1995). Grystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing. EMBO I. 14, 2689-2699. 

The neurotrophin family includes NGF, BDNF, neurotrophin-3 (NT-3), NT-4/5, and NT-6. All neurotrophins are capable of binding to the p75 receptor each neurotrophin also binds to a specific Trk receptor. Trk is the receptor for NGF TrkB is the receptor for BDNF and NT-4, while TrkC is the receptor for NT-3. Neurotrophins secreted by cells protect neurons from apoptosis (Korsching, 1993 Lewin and Barde, 1996). Similarly, ciliary neurotrophic factor (CNTF), a structurally related type I cytokine and GDNF, structurally related to TGF-[3, each constitute a sub-family of neurotrophic factors. 

Panayotatos, N., Radziejewska, E., Acheson, A., Somogyi, R., Thadani, A., Hendrickson, W.A., McDonald, N.Q., 1995. Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines. J. Biol. Chem. 270 (23), 14007-14014. 

Bok D, Yasumura D, Matthes M, et al. Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/ peripherin mutation. Exp Eye Res 2002 74 719-735. 

Carroll, P., Sendtner, M., Meyer, M. and Thoenen, H. (1993) Rat ciliary neurotrophic factor (CNTF) gene structure and regulation of mRNA levels in glial cell cultures. Glia 9 176-187. 

Lam, A., Fuller, F., Miller, J., Kloss, J., Manthorpe, M., Varon, S. and Cordell, B. (1991) Sequence and structural organization of the human gene encoding ciliary neurotrophic factor. Gene 102 271-276. 

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