Novel Mechanisms in the Regulation of G Protein-coupled Receptor Trafficking to the Plasma Membrane*
| Autor: | Louis M. Luttrell, Daniel J. Fernandes, Kusumam Joseph, Karthikeyan Kandasamy, John R. Raymond, Aleksander Baldys, Paul J. McDermott, Baby G. Tholanikunnel |
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| Rok vydání: | 2010 |
| Předmět: |
CHO Cells
Plasma protein binding Protein Sorting Signals Biology Models Biological Biochemistry ELAV-Like Protein 1 Receptors G-Protein-Coupled Cell membrane Cricetulus Cell surface receptor Cell Line Tumor Cricetinae Polysome Cell cortex medicine Animals Humans Receptor Molecular Biology Integral membrane protein G protein-coupled receptor Cell Membrane RNA-Binding Proteins Biological Transport Cell Biology Cell biology medicine.anatomical_structure ELAV Proteins Polyribosomes Antigens Surface Receptors Adrenergic beta-2 Signal Transduction Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 285:33816-33825 |
| ISSN: | 0021-9258 |
| Popis: | β(2)-adrenergic receptors (β(2)-AR) are low abundance, integral membrane proteins that mediate the effects of catecholamines at the cell surface. Whereas the processes governing desensitization of activated β(2)-ARs and their subsequent removal from the cell surface have been characterized in considerable detail, little is known about the mechanisms controlling trafficking of neo-synthesized receptors to the cell surface. Since the discovery of the signal peptide, the targeting of the integral membrane proteins to plasma membrane has been thought to be determined by structural features of the amino acid sequence alone. Here we report that localization of translationally silenced β(2)-AR mRNA to the peripheral cytoplasmic regions is critical for receptor localization to the plasma membrane. β(2)-AR mRNA is recognized by the nucleocytoplasmic shuttling RNA-binding protein HuR, which silences translational initiation while chaperoning the mRNA-protein complex to the cell periphery. When HuR expression is down-regulated, β(2)-AR mRNA translation is initiated prematurely in perinuclear polyribosomes, leading to overproduction of receptors but defective trafficking to the plasma membrane. Our results underscore the importance of the spatiotemporal relationship between β(2)-AR mRNA localization, translation, and trafficking to the plasma membrane, and establish a novel mechanism whereby G protein-coupled receptor (GPCR) responsiveness is regulated by RNA-based signals. |
| Databáze: | OpenAIRE |
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