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) undergoes palmitoylation at cysteine residues 621 and 622 located in the carboxyl terminal tail of the receptor. This study examined the biological function of palmitoylation with respect to its effect on receptor internalization. Coexpression of wild-type (WT) or C621/622G mutant receptors with arrestin-2 increased receptor internalization in 293T cells. Furthermore, measurements of rate enhancement upon overexpression of arrestin indicate that the palmitoylation deficient mutant receptor is more prone to utilizing the arrestin mediated internalization pathway than the WT receptor. Coexpression of G-protein-coupled receptor kinase 4 (GRK4) with wild type receptor resulted in an increase in internalization, while coexpression with the mutant receptor did not result in further enhancement of internalization. Additionally, 293T cells expressing mutant receptor were responsive to hCG with respect to production of inositol phosphates. Taken together, these results suggest that the palmitoylation state of the receptor governs internalization by regulating the accessibility of the receptor to the arrestin-mediated internalization pathway.
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA.
U M
UM
Munshi
H
H
Peegel
K M
KM
Menon
D019393:Arrestin / Q000378:metabolism*; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004705:Endocytosis; D054771:G-Protein-Coupled Receptor Kinase 4; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D009154:Mutation; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019393:Arrestin; D006063:Chorionic Gonadotropin; D007295:Inositol Phosphates; D011974:Receptors, LH; D019308:Palmitic Acid; D017346:Protein Serine-Threonine Kinases; D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human; D013755:Tetradecanoylphorbol Acetate