Modulation of postendocytic sorting of G protein-coupled receptors.
Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding ... protein (G protein)-coupled receptor-associated sorting protein (GASP). Disruption of the DOR-GASP interaction through receptor mutation or overexpression of a dominant negative fragment of GASP inhibited receptor trafficking to lysosomes and promoted recycling. The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein-coupled receptors.
Mesh Terms:
Animals, Carrier Proteins, Cell Division, Cell Line, Cell Membrane, Cell Survival, Down-Regulation, Endocytosis, Heterotrimeric GTP-Binding Proteins, Humans, Lysosomes, Mice, Microscopy, Fluorescence, Protein Transport, Receptor, Epidermal Growth Factor, Receptors, Adrenergic, beta-2, Receptors, Cell Surface, Receptors, Opioid, delta, Receptors, Opioid, mu, Recombinant Fusion Proteins, Transfection, Two-Hybrid System Techniques, Ubiquitin, Vesicular Transport Proteins
Animals, Carrier Proteins, Cell Division, Cell Line, Cell Membrane, Cell Survival, Down-Regulation, Endocytosis, Heterotrimeric GTP-Binding Proteins, Humans, Lysosomes, Mice, Microscopy, Fluorescence, Protein Transport, Receptor, Epidermal Growth Factor, Receptors, Adrenergic, beta-2, Receptors, Cell Surface, Receptors, Opioid, delta, Receptors, Opioid, mu, Recombinant Fusion Proteins, Transfection, Two-Hybrid System Techniques, Ubiquitin, Vesicular Transport Proteins
Science
Date: Jul. 26, 2002
PubMed ID: 12142540
View in: Pubmed Google Scholar
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