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 β2 adrenergic receptor and a mutant μ 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 (US) |
|---|---|
| Pages (from-to) | 29178-29185 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 282 |
| Issue number | 40 |
| DOIs | |
| State | Published - Oct 5 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Changes in G protein-coupled receptor sorting protein affinity regulate postendocytic targeting of G protein-coupled receptors. / Thompson, Dawn; Pusch, Margareta; Whistler, Jennifer.
In: Journal of Biological Chemistry, Vol. 282, No. 40, 05.10.2007, p. 29178-29185.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Changes in G protein-coupled receptor sorting protein affinity regulate postendocytic targeting of G protein-coupled receptors
AU - Thompson, Dawn
AU - Pusch, Margareta
AU - Whistler, Jennifer
PY - 2007/10/5
Y1 - 2007/10/5
N2 - 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 β2 adrenergic receptor and a mutant μ 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.
AB - 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 β2 adrenergic receptor and a mutant μ 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=35748974181&partnerID=8YFLogxK
U2 - 10.1074/jbc.M704014200
DO - 10.1074/jbc.M704014200
M3 - Article
C2 - 17635908
AN - SCOPUS:35748974181
VL - 282
SP - 29178
EP - 29185
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 40
ER -