G protein-coupled receptors: the inside story

Bioessays. 2010 Jan;32(1):13-6. doi: 10.1002/bies.200900153.


Recent findings necessitate revision of the traditional view of G protein-coupled receptor (GPCR) signaling and expand the diversity of mechanisms by which receptor signaling influences cell behavior in general. GPCRs elicit signals at the plasma membrane and are then rapidly removed from the cell surface by endocytosis. Internalization of GPCRs has long been thought to serve as a mechanism to terminate the production of second messengers such as cAMP. However, recent studies show that internalized GPCRs can continue to either stimulate or inhibit cAMP production in a sustained manner. They do so by remaining associated with their cognate G protein subunit and adenylyl cyclase at endosomal compartments. Once internalized, the GPCRs produce cellular responses distinct from those elicited at the cell surface.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cyclic AMP / metabolism
  • Endocytosis
  • Endosomes / metabolism
  • Fluorescence Resonance Energy Transfer
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Receptor, Parathyroid Hormone, Type 1 / metabolism
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Thyrotropin / metabolism
  • Signal Transduction


  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, G-Protein-Coupled
  • Receptors, Thyrotropin
  • Cyclic AMP