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 (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.
Pawson
A J
AJ
Department of Chemical Pathology, University of Cape Town Medical School, Observatory, South Africa.
Katz
A
A
Sun
Y M
YM
Lopes
J
J
Illing
N
N
Millar
R P
RP
Davidson
J S
JS
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
C111973:LHRH, His(5)-Tyr(6)-; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone