Beneath the surface: endosomal GPCR signaling

Emmanuel Flores-Espinoza, Alex R.B. Thomsen

Research output: Contribution to journalReview articlepeer-review


G protein-coupled receptors (GPCRs) located at the cell surface bind extracellular ligands and convey intracellular signals via activation of heterotrimeric G proteins. Traditionally, G protein signaling was viewed to occur exclusively at this subcellular region followed by rapid desensitization facilitated by β-arrestin (βarr)-mediated G protein uncoupling and receptor internalization. However, emerging evidence over the past 15 years suggests that these βarr-mediated events do not necessarily terminate receptor signaling and that some GPCRs continue to activate G proteins after having been internalized into endosomes. Here, we review the recently elucidated mechanistic basis underlying endosomal GPCR signaling and discuss physiological implications and pharmacological targeting of this newly appreciated signaling mode.

Original languageEnglish (US)
JournalTrends in Biochemical Sciences
StateAccepted/In press - 2024


  • GPCR: G protein, β-arrestin
  • desensitization
  • endosomal signaling
  • megaplexes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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