Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFL) are potent survival factors and regulators for central and peripheral neurons. GFLs bind to specific glycosyl phosphatidylinositol (GPI)-anchored co-receptors (GFRalpha1-alpha4), but signal through a common c-Ret receptor. Both GPI-anchored and soluble GFRalpha1 recruit c-Ret to lipid rafts following GDNF stimulation, where c-Ret interacts with different proteins than outside the rafts. Soluble GFRalpha1 mobilizes c-Ret to rafts by a different mechanism compared with GPI-anchored GFRalpha1.
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