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Updated: May 9, 2026

Detection of G Protein-coupled Receptor Expression in Mouse Vagal Afferent Neurons using Multiplex In Situ Hybridization
Published on: September 20, 2021
Species sequence differences determine the interaction of GnRH receptor with the cellular quality control system
Alejandro Cabrera-Wrooman1, Jo Ann Janovick, P Michael Conn
1Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
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.
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