CDB15:0000297 CGA — LHCGR
Experimentally validated in Human, Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
The alpha-subunit of human choriogonadotropin interacts with the exodomain of the luteinizing hormone/choriogonadotropin receptor.
Endocrinology, 1999; PubMed, Homo sapiens CGA — Rattus norvegicus Lhcgr
ABSTRACT: The LH/CG receptor, a G protein-coupled receptor, consists of two parts, the N-terminal extracellular segment (exodomain) and the membrane-associated C-terminal segment (endodomain). hCG initially binds the exodomain of the receptor and then, the hormone/exodomain complex is thought to make the secondary contact with the endodomain of the receptor and generate a hormone signal. However, little direct evidence is available about which hormone subunits (alpha or beta) interact with which domains of the receptor. To determine whether the alpha-subunit contacts the exodomain of its receptor, hCG containing [125I]alpha and truncated exodomain lacking the endodomain were prepared. They were chemically cross-linked, and the resulting cross-linked complexes were solubilized and electrophoresed. The results indicate that the alpha-subunit of hCG was directly and specifically cross-linked to the exodomain. To verify the cross-linked exodomain by the independent method, the Flag epitope was inserted between the signal sequence and the mature exodomain. hCG containing [125I]alpha was cross-linked to the Flag exodomain, and the resulting cross-linked hCG/Flag exodomain complexes were immunoprecipitated with anti-Flag antibody. The results show that the material cross-linked to hCG containing [125I]alpha is indeed the exodomain. In conclusion, our results show the direct interaction of the alpha-subunit with the exodomain and, therefore, its crucial role in the hormone-receptor interaction in addition to its involvement in signal generation.
Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action.
The Journal of clinical endocrinology and metabolism, 2003; PubMed, Homo sapiens CGA — Homo sapiens LHCGR
ABSTRACT: The LH receptor (LHR) mediates the actions of LH and human chorionic gonadotropin (hCG). In vivo data showed that deletion of exon 10 does not affect hCG action, whereas LH action is impaired. To investigate the role of exon 10 in LH/hCG action in vitro we created stable COS-7 cells expressing the LHR with (wt) or without (-ex10) exon 10. Binding experiments showed that the affinities of LH and hCG to the LHR wt and -ex10 were similar. Stimulation of wt with hCG or LH resulted in increased cAMP. cAMP production was significantly impaired in -ex10 stimulated with LH. This response was not altered by pertussis toxin, excluding that G(i) becomes activated in LHR -ex10. In desensitization experiments, intracellular cAMP of LHR wt and -ex10 declined to approximately 30%. No difference in intracellular cAMP was detected between LHR wt or -ex10 after recovery and restimulation with hCG or LH. These experiments show that impaired cAMP production of LHR -ex10 stimulated with LH is not due to anomalous receptor coupling or desensitization. We conclude that although exon 10 of the LHR plays no role in ligand binding, it is important for receptor activation by LH by a mechanism probably involving extracellular conformational changes.