Protein disulfide isomerase chaperone ERP‐57 decreases plasma membrane expression of the human GnRH receptor |
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| Authors: | Rodrigo Ayala Yáñez P Michael Conn |
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| Institution: | 1. Divisions of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA;2. Division of Reproductive Biology, Oregon National Primate Research Center, Beaverton, Oregon, USA;3. Departments of Physiology and Pharmacology, Cell and Developmental Biology and Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA |
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| Abstract: | Retention of misfolded proteins by the endoplasmic reticulum (ER) is a quality control mechanism involving the participation of endogenous chaperones such as calnexin (CANX). CANX interacts with and restricts plasma membrane expression (PME) of the gonadotropin releasing hormone receptor (GnRHR), a G protein‐coupled receptor. CANX also interacts with ERP‐57 a thiol oxidoreductase chaperone present in the ER. CANX along with ERP‐57 promotes the formation of disulfide bond bridges in nascent proteins. The human GnRH receptor (hGnRHR) is stabilized by two disulfide bond bridges (C14‐C200 and C114‐C196), that, when broken, lead to a decrease in receptor expression at the plasma membrane. To determine if the presence of chaperones CANX and ERP‐57 exerts an influence over membrane routing and second messenger activation, we assessed the effect of various mutants including those with broken disulfide bridges (Cys → Ala) along with the hGnRHR. The effect of chaperones on mutants was insignificant, whereas the over expression of ERP‐57 led to an hGnRHR retention. This effect was further enhanced by cotransfection with cDNA for CANX showing receptor retention by ERP‐57 augmented by CANX, suggesting utilization of these chaperones for quality control of the GnRHR. Copyright © 2009 John Wiley & Sons, Ltd. |
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| Keywords: | hormone action GPCR protein folding GnRH receptor protein retention chaperone |
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