title: Species sequence differences determine the interaction of GnRH receptor with the cellular quality control system.
abstract: Plasma membrane expression (PME) of the human GnRHR (hGnRHR) is regulated by a primate-specific Lys(191) which destabilizes a Cys(14)-Cys(200) bridge required by the cellular quality control system (QCS). A 4-amino, non-contiguous "motif" (Leu(112), Gln(208), Leu(300), Asp(302)) is required for this effect. The hGnRHR sequence, with or without Lys(191), decreases PME and inositol phosphate (IP) production when co-expressed with calnexin, a QCS chaperone. WT rat GnRHR, decreases PME and IP production, when co-expressed with calnexin, but to a lesser degree than hGnRH. When the human sequence contains the rat motif, IP production is closer to that of rat GnRHR. When Lys(191) is deleted from hGnRHR and co-expressed with calnexin, IP production is similar to the rat sequence. When rat GnRHR containing Lys(191) and the human motif is co-expressed with calnexin, IP production is similar to cells expressing the hGnRHR. The motif sequence appears to be a determinant of calnexin recognition.
authors.affiliation: Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. Electronic address: aca_w@yahoo.com.mx.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cabrera-Wrooman
authors.forename: Jo Ann
authors.initials: JA
authors.lastname: Janovick
authors.forename: P Michael
authors.initials: PM
authors.lastname: Conn
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002064:Buserelin / Q000494:pharmacology; D019556:COS Cells; D037281:Calnexin / Q000378:metabolism; D002462:Cell Membrane; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007295:Inositol Phosphates / Q000378:metabolism; D008239:Lysine / Q000235:genetics; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats; D011966:Receptors, LHRH / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D007295:Inositol Phosphates; D011966:Receptors, LHRH; D037281:Calnexin; D008239:Lysine; D002064:Buserelin
keywords: Calnexin; ER protein retention; GPCR; GnRH receptor; Protein trafficking
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