Glial-Derived Neurotrophic Factor (GDNF) Family Receptors

The GDNF family ligands (GFLs) belong to the super family of the TGF-β. They belong to the group of cystine-knot protein and function as homodimers. This family includes glial cell line-derived neurotrophic factor (GDNF), artemin (ARTN), Neurturin (NRTN) and persephin (PSPN). These factors are heavily involved in the development and function of the nervous system (both central and peripheral). In general GFLs all signal through a signal through the receptor tyrosine kinase Ret. Their specificity is implemented by different GDNF family receptor α (GFRα), which act as co-receptors. These extracellular proteins are bound to the plasma membrane via a glycosyl phosphatidyl inositol (GPI) anchor. GFRα1-4 are responsible for the binding of GDNF, NRTN, ARTN, and PSPN respectively and the subsequent activation of Ret.