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Protein disulfide isomerase chaperone ERP‐57 decreases plasma membrane expression of the human GnRH receptor
Author(s) -
Yáñez Rodrigo Ayala,
Conn P. Michael
Publication year - 2010
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1622
Subject(s) - protein disulfide isomerase , endoplasmic reticulum , calnexin , gnrhr , chaperone (clinical) , receptor , microbiology and biotechnology , chemistry , gonadotropin releasing hormone receptor , chemical chaperone , g protein coupled receptor , biochemistry , gonadotropin releasing hormone , biology , unfolded protein response , hormone , calreticulin , medicine , pathology , luteinizing hormone
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 (C 14 ‐C 200 and C 114 ‐C 196 ), 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.