GDNF family receptors (GFR) are extrinsic co-receptors, where ligand binding to the extracellular domain of the glycosylphosphatidylinositol-linked cell-surface GFRs activates a transmembrane tyrosine kinase enzyme, RET. The endogenous ligands are typically dimeric, linked through disulphide bridges: glial cell-derived neurotrophic factor GDNF (GDNF, P39905) (211 aa); neurturin (NRTN, Q99748) (197 aa); artemin (ARTN, Q5T4W7) (237 aa) and persephin (PSPN, O60542) (156 aa), referred to as GDNF family ligands (GFLs). There is evidence for RET-dependent and RET-independent signalling [4]. Growth/Differentiation Factor 15 (GDF15) has been shown to activate GFRAL, a transmembrane protein that similarly forms a complex with RET [7,9].

* Key recommended reading is highlighted with an asterisk

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Chloe J. Peach Division of Physiology, Pharmacology & Neuroscience School of Life Sciences, Centre of Membrane Proteins and Receptors (COMPARE) University of Nottingham Medical School Nottingham NG7 2UH UK