Palmitoylation of the luteinizing hormone/human chorionic gonadotropin receptor regulates receptor interaction with the arrestin-mediated internalization pathway

The luteinizing hormone/human chorionic gonadotropin receptor (LH/hCGR) und ergoes palmitoylation at cysteine residues 621 and 622 located in the carbo xyl terminal tail of the receptor. This study examined the biological funct ion of palmitoylation with respect to its effect on receptor internalizatio n. Coexpression of wild-type (WT) or C621/622G mutant receptors with arrest in-2 increased receptor internalization in 293T cells. Furthermore, measure ments of rate enhancement upon overexpression of arrestin indicate that the palmitoylation deficient mutant receptor is more prone to utilizing the ar restin mediated internalization pathway than the WT receptor. Coexpression of G-protein-coupled receptor kinase 4 (GRK4) with wild type receptor resul ted in an increase in internalization, while coexpression with the mutant r eceptor did not result in further enhancement of internalization. Additiona lly, 293T cells expressing mutant receptor were responsive to hCG with resp ect to production of inositol phosphates. Taken together, these results sug gest that the palmitoylation state of the receptor governs internalization by regulating the accessibility of the receptor to the arrestin-mediated in ternalization pathway.