G protein-coupled receptor-associated sorting protein 1 regulates the postendocytic sorting of seven-transmembrane-spanning G protein-coupled receptors

Elisabeth Moser, Julia Kargl, Jennifer Whistler, Maria Waldhoer, Pia Tschische

Research output: Contribution to journalReview article

29 Scopus citations

Abstract

The largest superfamily of membrane proteins that translate extracellular signals into intracellular messages are the 7-transmembrane-spanning (7TM) G protein-coupled receptors (GPCR). One of the ways in which their activity is controlled is by the process of desensitization and endocytosis, whereby agonist-activated receptors are rapidly and often reversibly silenced through removal from the cell surface. Indeed, following endocytosis, individual receptors can be sorted differentially between recycling endosomes and lysosomes, which controls the reversibility of the silencing. Thus, endocytosis can either serve as a mechanism for receptor resensitization by delivering receptors back to the plasma membrane or facilitate receptor downregulation by serving as the first step towards targeting the receptors to lysosomes for degradation. The sorting of receptors to the lysosomal pathway can be facilitated by interaction with an array of accessory proteins. One of these proteins is the GPCR-associated sorting protein 1 (GASP-1), which specifically targets several 7TM-GPCR to the lysosomal pathway after endocytosis. Furthermore, GASP-1 was recently found to directly affect the signaling capacity of a 7TM-GPCR. Importantly, the in vivo relevance of GASP-1-dependent receptor sorting has also begun to be verified in animal models. Here, we summarize the recent advances in elucidating GASP-1-dependent receptor sorting functions and their potential implications in vivo.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalPharmacology
Volume86
Issue number1
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

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Keywords

  • Adaptor protein
  • Degradation
  • G protein-coupled receptor-associated sorting protein 1
  • G protein-coupled receptor-associated sorting protein 2
  • Postendocytic receptor sorting
  • Receptor, downregulation
  • Seven-transmembrane domain G protein-coupled receptor
  • Trafficking

ASJC Scopus subject areas

  • Pharmacology

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