Targeting of G protein-coupled receptors to the plasma membrane in health and disease.
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.
Ulloa-Aguirre
Alfredo
A
Research Unit in Reproductive Medicine, Hospital de Ginecobstetricia, Luis Castelazo Ayala, Instituto Mexicano del Seguro Social, Mexico DF, Mexico.
Conn
P Michael
PM
D000818:Animals; D001704:Biopolymers; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D017510:Protein Folding; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*
D001704:Biopolymers; D043562:Receptors, G-Protein-Coupled