Changes in G protein-coupled receptor sorting protein affinity regulate postendocytic targeting of G protein-coupled receptors

Dawn Thompson, Margareta Pusch, Jennifer Whistler

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)29178-29185
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number40
DOIs
StatePublished - Oct 5 2007
Externally publishedYes

Fingerprint

Protein Transport
G-Protein-Coupled Receptors
Sorting
Endocytosis
Degradation
Dopamine D1 Receptors
Proteins
Opioid Receptors
Recycling
Lysosomes
Adrenergic Receptors
Cell Membrane
Cell membranes
Mutation
Chemical activation

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 journalArticle

@article{130c80150f80414db28713f422b9c345,
title = "Changes in G protein-coupled receptor sorting protein affinity regulate postendocytic targeting of G protein-coupled receptors",
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.",
author = "Dawn Thompson and Margareta Pusch and Jennifer Whistler",
year = "2007",
month = "10",
day = "5",
doi = "10.1074/jbc.M704014200",
language = "English (US)",
volume = "282",
pages = "29178--29185",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "40",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=35748974181&partnerID=8YFLogxK

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 -