title: Contrasting internalization kinetics of human and chicken gonadotropin-releasing hormone receptors mediated by C-terminal tail.
abstract: The chicken gonadotropin-releasing hormone receptor (GnRH-R) is notable for having a cytoplasmic C-terminal tail, which is not present in the mammalian GnRH-Rs. We report here that the cytoplasmic tail mediates rapid agonist-promoted receptor internalization. The chicken GnRH-R mediated internalization of gonadotropin-releasing hormone (GnRH) agonist (125I[His5-D-Tyr6]GnRH) at a rate of 11.3%.min-1, compared with only 0.71 %.min-1 for the human GnRH-R. To determine whether the presence of the cytoplasmic tail was responsible for the more rapid internalization kinetics of the chicken GnRH-R we truncated the tail after the Ile336 residue (S337stop). Receptor-mediated internalization of GnRH agonist by the S337stop-chicken GnRH-R was much slower than in the wild-type chicken receptor, and was similar to the wild-type human GnRH-R (0.55 %.min-1). These data indicate that rapid agonist-promoted internalization of the chicken GnRH-R is mediated through elements in the cytoplasmic C-terminal tail, distal to or including Ser337 and suggests that elimination of the C-terminal tail during evolution of mammalian GnRH-Rs may be related to its effects on internalization.
authors.affiliation: Department of Chemical Pathology, University of Cape Town Medical School, Observatory, South Africa.
authors.forename: A J
authors.initials: AJ
authors.lastname: Pawson
authors.forename: A
authors.initials: A
authors.lastname: Katz
authors.forename: Y M
authors.initials: YM
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Lopes
authors.forename: N
authors.initials: N
authors.lastname: Illing
authors.forename: R P
authors.initials: RP
authors.lastname: Millar
authors.forename: J S
authors.initials: JS
authors.lastname: Davidson
mesh_terms: D000818:Animals; D002645:Chickens; D019143:Evolution, Molecular; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C111973:LHRH, His(5)-Tyr(6)-; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone