POSTTRANSLATIONAL PROCESSING IN THE GOLGI PLAYS A CRITICAL ROLE IN THE TRAFFICKING OF THE LUTEINIZING HORMONE HUMAN CHORIONIC-GONADOTROPIN RECEPTOR TO THE CELL-SURFACE/
Fa. Bradbury et al., POSTTRANSLATIONAL PROCESSING IN THE GOLGI PLAYS A CRITICAL ROLE IN THE TRAFFICKING OF THE LUTEINIZING HORMONE HUMAN CHORIONIC-GONADOTROPIN RECEPTOR TO THE CELL-SURFACE/, The Journal of biological chemistry, 272(9), 1997, pp. 5921-5926
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.