Conserved mammalian gonadotropin-releasing hormone receptor carboxyl terminal amino acids regulate ligand binding, effector coupling and internalization

Shaun P. Brothers, Jo Ann Janovick, Guadalupe Maya-Nunez, Anda Cornea, Xin Bing Han, P. Michael Conn

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    The mammalian gonadotropin-releasing hormone receptor (GnRHR), with 327 amino acids, is among the smallest G protein coupled receptors identified. Absent from this receptor is the cytoplasmic tail, characteristic of other members of this superfamily, which frequently mediates desensitization and down-regulation. The fifteen carboxyl terminal residues in the mammalian GnRHR are absolutely conserved, suggesting important roles for these residues. In the current study, mutations of the mammalian GnRHR were made to study the carboxyl terminus. The receptor mutant GnRHR(Ser326Ala) was reduced in ligand affinity (117% reduction compared to wild type (wt)), while receptor numbers and internalization remained unchanged. GnRHR(Ser326Tyr) was decreased in effector coupling, while ligand affinity remained unchanged compared to wt. These studies also show that, while mutation of Ser326 caused a change in ligand binding and effector coupling, truncation at this residue (GnRHR[des326-327]) had no measurable effect on GnRHR ligand binding, effector coupling or internalization, functions which appear to require different structural determinants than expression and routing. Removal of all three carboxyl terminal residues (Phe325, Ser326 and Leu327) or mutation of the receptor (GnRHR[Phe325Ala]) caused a complete loss of measurable ligand binding and effector coupling, clearly suggesting an unexplained role for Phe325.

    Original languageEnglish (US)
    Pages (from-to)19-27
    Number of pages9
    JournalMolecular and Cellular Endocrinology
    Issue number1-2
    Publication statusPublished - Apr 25 2002



    • G protein coupling
    • GnRH receptor
    • Gonadotropin-releasing hormone

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism

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