POSTTRANSLATIONAL PROCESSING IN THE GOLGI PLAYS A CRITICAL ROLE IN THE TRAFFICKING OF THE LUTEINIZING HORMONE HUMAN CHORIONIC-GONADOTROPIN RECEPTOR TO THE CELL-SURFACE/

Point mutations in the luteinizing hormone/human chorionic gonadotropi n (LH/hCG) receptor have been shown to cause constitutive activation w hich results in precocious puberty in affected males, We introduced on e of these mutations, Asp-556 --> Gly, into the rat LH/hCG receptor an d demonstrated that the mutant receptor constitutively activated adeny late cyclase in transfected 293 T cells. The cell surface expression o f the mutant receptor was lower than that of the wild type receptor, P ulse-chase studies showed that the 73-kDa precursor of both the mutant and wild type receptors was synthesized at comparable efficiencies. H owever, post-translational processing of the mutant receptor to the ma ture 92-kDa form, which has N-linked complex type oligosaccharide chai ns, was impaired. Sensitivity of the mutant receptor to peptide-N-glyc anase F and endoglycosidase H, and insensitivity to sialidase indicate d that the 73-kDa species represents the high mannose form that has no t yet been trafficked through the medial and trans Golgi. Additionally , although time wild type receptor was palmitoylated, the mutant recep tor was not. Although the high mannose 73-kDa species is capable of bi nding LH/hCG, our results show that post-translational processing in t he Golgi is required for the mature 92-kDa receptor to reach the cell surface.