Role of asparagine-linked oligosaccharides in the function of the rat PTH/PTHrP receptor

The receptor for parathyroid hormone (PTH) and PTH-related peptide (PHrP) i s a G-protein-coupled receptor with four potential sites for N-linked glyco sylation. The contribution of the oligosaccharide moieties to cell surface expression, ligand binding, and signal transduction was investigated. Site- directed mutagenesis of the rat PTH/PTHrP receptor cDNA was performed at si ngle or combination of the four potential glycosylation sites to determine the effect of the putative carbohydrate chains on the activities of the rec eptor. The results revealed that all four potential N-glycosylation sites i n the PTH/PTHrP receptor are glycosylated. Receptors missing a single or mu ltiple glycosylation consensus but with at least one intact glycosylation s ite expressed sufficiently and functioned normally. In contrast, the nongly cosylated receptor, in which all four glycosylation sites were mutated, is deficient in these functions. These data indicate important roles for N-lin ked glycosylation in PTH/PTHrP receptor functions.