Therapeutic Targeting of Endosomal G-Protein-Coupled Receptors

Alex R.B. Thomsen, Dane D. Jensen, Gareth A. Hicks, Nigel W. Bunnett

Research output: Contribution to journalReview articlepeer-review


G-protein-coupled receptors (GPCRs) are conventionally considered to function at the plasma membrane, where they detect extracellular ligands and activate heterotrimeric G proteins that transmit intracellular signals. Consequently, drug discovery efforts have focused on identification of agonists and antagonists of cell surface GPCRs. However, β-arrestin (ARR)-dependent desensitization and endocytosis rapidly terminate G protein signaling at the plasma membrane. Emerging evidence indicates that GPCRs can continue to signal from endosomes by G-protein- and βARR-dependent processes. By regulating the duration and location of intracellular signaling events, GPCRs in endosomes control critically important processes, including gene transcription and ion channel activity. Thus, GPCRs in endosomes, in addition to at the cell surface, have emerged as important therapeutic targets.

Original languageEnglish (US)
Pages (from-to)879-891
Number of pages13
JournalTrends in Pharmacological Sciences
Issue number10
StatePublished - Oct 2018


  • compartmentalized signaling
  • endosomes
  • receptor trafficking

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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