Regulation of GPCR signal networks via membrane trafficking

Mol Cell Endocrinol. 2011 Jan 15;331(2):205-14. doi: 10.1016/j.mce.2010.07.010. Epub 2010 Jul 21.


G-protein-coupled receptors (GPCRs) are a superfamily of cell surface signaling proteins that act as central molecular activators and integrators in all endocrine systems. Membrane trafficking of GPCRs is a fundamental process in shaping extensive signaling networks activated by these receptors. Mounting evidence has identified an increasingly complex network of pathways and protein interactions that a GPCR can traverse and associate with, indicating a multi-level system of regulation. This review will discuss the recent developments in how GPCRs are trafficked to the cell surface as newly synthesized receptors, their recruitment to the clathrin-mediated pathway for endocytosis, and their sorting to subsequent divergent post-endocytic fates, focusing primarily on hormone-activated GPCRs. Current models depicting the classic roles membrane trafficking plays in GPCR signaling have evolved to a highly regulated and complex system than previously appreciated. These developments impart key mechanistic information on how spatial and temporal aspects of GPCR signaling may be integrated and could provide pathway-specific targets to be exploited for therapeutic intervention.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Endocytosis
  • Humans
  • Membrane Proteins / metabolism*
  • Protein Transport
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction


  • Membrane Proteins
  • Receptors, G-Protein-Coupled