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Papers In Press, published online ahead of print May 18, 2005
Anatomy and Cell Biology, University of Oulu, Oulu FI-90014
Corresponding Author: Ulla.Petaja-Repo{at}oulu.fi
Increasing evidence suggests that folding and maturation of monomeric proteins and assembly of multimeric protein complexes in the endoplasmic reticulum (ER) may be inefficient not only for mutants that carry changes in the primary structure but also for wild type proteins. In the present study, we demonstrate that the rat luteinizing hormone receptor (LHR), a G protein-coupled receptor, is one of these proteins that matures inefficiently and appears to be very prone to premature degradation. A substantial portion of the LHRs in stably transfected human embryonic kidney 293 cells existed in immature form of Mr 73,000, containing high mannose type N-linked glycans. In metabolic pulse-chase studies, only about 20% of these receptor precursors were found to gain hormone-binding ability and matured to a form of Mr 90,000, containing bi- and multiantennary sialylated N-linked glycans. The rest had a propensity to form disulfide-bonded complexes with a Mr 120,000 protein in the ER membrane and were eventually targeted for degradation in proteasomes. The number of membrane-bound receptor precursors increased when proteasomal degradation was inhibited and no cytosolic receptor forms were detected, suggesting that retrotranslocation of the misfolded/incompletely folded receptors is tightly coupled to proteasomal function. Furthermore, proteasomal blockade was found to increase the number of receptors that were capable of hormone binding. Thus, these results raise the interesting possibility that LHR expression at the cell surface may be controlled at the ER level by regulating the number of newly synthesized proteins that will mature and escape the ER quality control and premature degradation.
J. Biol. Chem, 10.1074/jbc.M413815200
Submitted on December 8, 2004
Accepted on May 18, 2005
Inefficient maturation of the rat luteinizing hormone receptor: A putative way to regulate receptor numbers at the cell surface
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