IMR Press / FBL / Volume 14 / Issue 3 / DOI: 10.2741/3290

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Targeting of G protein-coupled receptors to the plasma membrane in health and disease
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1 Research Unit in Reproductive Medicine, Hospital de Ginecobstetricia “Luis Castelazo Ayala”, Instituto Mexicano del Seguro Social, Mexico D.F., Mexico
2 Oregon National Primate Research Center, Beaverton, OR, USA
3 Departments of Physiology and Pharmacology, and Cell and Developmental Biology, Oregon Health & Science University, Portland, OR, USA
Front. Biosci. (Landmark Ed) 2009, 14(3), 973–994;
Published: 1 January 2009

G protein-coupled receptors (GPCRs) are cell surface membrane proteins that recognize specific signals (ligands) from an immense number of chemically diverse substances. These receptors act as signal transducers for messages carried by external, systemic, or local stimuli. As complex molecular structures, which must attain specific shapes, newly synthesized GPCRs are subjected to conformational scrutiny at the endoplasmic reticulum level before their passage to the plasma membrane. Such a quality control mechanism guards against aberrant protein structures and checks for proper folding, processing and structural integrity of nascent proteins. Despite this stringent quality control screening mechanism, gain- or loss-of-function mutations that result in GPCR misfolding in the endoplasmic reticulum can manifest themselves as profound effects on health. Understanding the molecular, cellular and energetic mechanisms controlling GPCR intracellular routing is essential for preventing or correcting the conformational abnormalities associated with disease-causing misfolded receptors. This article reviews the mechanisms subserving plasma membrane targeting of GPCRs and describes novel and promising approaches to correct misfolding and misrouting related to various disease states.

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