Abstract
After activation, most G protein-coupled receptors (GPCRs) are regulated by a cascade of events involving desensitization and endocytosis. Internalized receptors can then be recycled to the plasma membrane, retained in an endosomal compartment, or targeted for degradation. The GPCR-associated sorting protein, GASP, has been shown to preferentially sort a number of native GPCRs to the lysosome for degradation after endocytosis. Here we show that a mutant beta(2) adrenergic receptor and a mutant mu opioid receptor that have previously been described as lacking "recycling signals" due to mutations in their C termini in fact bind to GASP and are targeted for degradation. We also show that a mutant dopamine D1 receptor, which has likewise been described as lacking a recycling signal, does not bind to GASP and is therefore not targeted for degradation. Together, these results indicate that alteration of receptors in their C termini can expose determinants with affinity for GASP binding and consequently target receptors for degradation.
Original language | English |
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Pages (from-to) | 29178-85 |
Number of pages | 8 |
Journal | The Journal of Biological Chemistry |
Volume | 282 |
Issue number | 40 |
DOIs | |
Publication status | Published - 5 Oct 2007 |
Keywords
- Biotin
- Cell Line
- Endocytosis
- Gene Expression Regulation
- Humans
- Mutation
- Protein Binding
- Protein Structure, Tertiary
- Protein Transport
- Receptors, Adrenergic, beta-2
- Receptors, Dopamine D1
- Receptors, G-Protein-Coupled
- Receptors, Opioid, mu
- Signal Transduction
- Transferrin