Contrasting internalization kinetics of human and chicken Gonadotropin-Releasing Hormone Receptors mediated by C-terminal tail

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 (I-125-[His(5)-D-Tyr(6)]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 Ile(336) 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 hi the cytoplasmic C-terminal tail, distal to or including Ser(337) and suggests that elimination of the C-terminal tail during evolution of mammalian GnRH-Rs may be related to its effects on internalization.