The trick of the tail: protein-protein interactions of metabotropic glutamate receptors

Bioessays. 2007 Jan;29(1):60-73. doi: 10.1002/bies.20518.


It was initially believed that G-protein-coupled receptors, such as metabotropic glutamate receptors, could simply be described as individual proteins that are associated with intracellular signal cascades via G-proteins. This view is no longer tenable. Today we know that metabotropic glutamate receptors (mGluRs) can dimerize and bind to a variety of proteins in addition to trimeric G-proteins. These newly identified protein interactions led to the discovery of new regulatory mechanisms that are independent of and sometimes synergistic with the classical G-protein-coupled second messenger pathways. Notably, several of these mechanisms connect mGluR-mediated signaling to other receptor classes, thereby creating a network of different receptor types and associated signal cascades. The intracellular C-termini of mGluRs play a key role in the regulation of these networks, and various new protein interactions of these domains were described recently. Because mGluRs are involved in a variety of physiological and pathophysiological processes, some of the proteins interacting with this receptor class have potential as valuable pharmaceutical targets. This review will give a comprehensive overview of proteins interacting with mGluR C-termini, highlight new evolving regulatory mechanisms for glutamatergic signal transduction and discuss possibilities for future drug development.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Microdomains / metabolism
  • Membrane Proteins / metabolism
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Protein Binding
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Sequence Homology, Amino Acid
  • Static Electricity


  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Multiprotein Complexes
  • Receptors, Metabotropic Glutamate