Evidence for the presence of a critical disulfide bond in the mouse EP3γ receptor

▶ Mutation of each cysteine residue of the mouse EP3 receptor to alanine was performed. ▶ 11 of the substitutions were well tolerated in terms of radioligand binding and receptor signaling. ▶ Two residues, when individually mutated, result in a loss of ligand binding, signal transduction and a dramatic decrease in receptor protein expression and trafficking to the cell surface. ▶ These results suggest the presence of a critical disulfide bond between Cys 106 and Cys 187. This is in contrast to the rabbit receptor ortholog where mutation of the Cys 187 position has no effect on ligand binding or signal transduction.