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

Dawn Thompson, Margareta Pusch, Jennifer L 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 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 languageEnglish
Pages (from-to)29178-85
Number of pages8
JournalThe Journal of Biological Chemistry
Volume282
Issue number40
DOIs
Publication statusPublished - 5 Oct 2007

Fingerprint

Protein Transport
G-Protein-Coupled Receptors
Sorting
Endocytosis
Degradation
Adrenergic beta-2 Receptors
Dopamine D1 Receptors
Proteins
mu Opioid Receptor
Recycling
Lysosomes
Cell Membrane
Cell membranes
Mutation
Chemical activation

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

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 L.

In: The Journal of Biological Chemistry, Vol. 282, No. 40, 05.10.2007, p. 29178-85.

Research output: Contribution to journalArticle

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