Postendocytic Sorting of Adrenergic and Opioid Receptors: New Mechanisms and Functions

Prog Mol Biol Transl Sci. 2015;132:189-206. doi: 10.1016/bs.pmbts.2015.03.005. Epub 2015 Apr 11.

Abstract

The endocytic pathway tightly regulates the activity of G protein-coupled receptors (GPCRs). Much of our understanding of this relationship between GPCR endocytic trafficking and signaling comes from studies done on catecholamine and opioid receptors. After ligand-induced endocytosis, a key sorting step in the endosome determines whether receptors are recycled back to the cell surface, leading to recovery of signaling, or are degraded in the lysosome, leading to desensitization. Recycling of GPCRs, unlike that of many other proteins, is an active process driven by specific sequences on the receptor and proteins that interact with this sequence. Recent data suggest that sequence-dependent recycling plays complex roles in regulating both the timing and location of GPCR signaling. This chapter will describe our current understanding of the mechanisms regulating GPCR sorting in the endosome and discuss emerging ideas on their role in GPCR signaling, focusing on adrenergic and opioid receptors as prototypes.

Keywords: Adrenergic; Endosome; GPCR; Kinetic sorting; Opioid; PDZ; Recycling; Sorting.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • Endocytosis*
  • Endosomes / metabolism
  • Humans
  • Ligands
  • Lysosomes / metabolism
  • Phosphorylation
  • Protein Transport
  • Receptors, Adrenergic / metabolism*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Opioid / metabolism*
  • Signal Transduction

Substances

  • Ligands
  • Receptors, Adrenergic
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid