Inefficient maturation of the rat luteinizing hormone receptor: A putative way to regulate receptor numbers at the cell surface

E. Maritta Pietilä, Jussi T. Tuusa, Pirjo Apaja, Jyrki T. Aatsinki, Anna E. Hakalahti, Hannu J. Rajaniemi, Ulla E. Petäjä-Repo

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Abstract

Increasing evidence suggests that the 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, 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 receptors 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 ∼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, a proteasomal blockade was found to increase the number of receptors that were capable of hormone binding. Thus, these results raise the interesting possibility that luteinizing hormone receptor 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.

LanguageEnglish
Pages26622-26629
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number28
DOIs
Publication statusPublished - 15 Jul 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Pietilä, E. M., Tuusa, J. T., Apaja, P., Aatsinki, J. T., Hakalahti, A. E., Rajaniemi, H. J., & Petäjä-Repo, U. E. (2005). Inefficient maturation of the rat luteinizing hormone receptor: A putative way to regulate receptor numbers at the cell surface. Journal of Biological Chemistry, 280(28), 26622-26629. https://doi.org/10.1074/jbc.M413815200