Abstract
A replacement of proline with leucine at position 132 of the receptor for parathyroid hormone(PTH)/parathyroid hormone-related peptide (PTHrP), i.e., PTH-R, has been discovered in patients carrying Blomstrand's lethal chondrodysplasia. As skeletal deformities in this type of chondrodysplasia appear to relate to compromised receptor binding to its ligand, we examined the possibility that rat PTH-R carrying P 132 L mutation (PTH-RP132L) would result in abnormal intracellular localization and transport, by transfecting cDNAs encoding either wild-type PTH-R or mutant PTH-RP132L.ThePTHRP132L was hardly detected on the cell surfaces, but accumulated within the rough-surfaced endoplasmic reticulum. Furthermore, a remarkably weaker intensity of the band compared with the wild-type counterpart suggests that PTH-RP132L is prone to degradation in the transfected cells. These findings indicate that defective transport of PTH-RP132L to the cell surface would be the molecular basis for Blomstrand's chondrodysplasia.
