Complementary roles of the DRY motif and C-terminus tail of GPCRS for G protein coupling and beta-arrestin interaction

Biochem Biophys Res Commun. 2008 Feb 1;366(1):42-7. doi: 10.1016/j.bbrc.2007.11.055. Epub 2007 Nov 26.

Abstract

beta-arrestin mediates the desensitization of GPCRs and acts as an adaptor molecule to recruit the receptor complex to clathrin-rich regions. Class-A GPCRs subsequently dissociate from beta-arrestin but class-B GPCRs internalize with beta-arrestin in the endocytic vesicles. Here the dopamine D(2) and D(3) receptors, which have similar structural features but different intracellular trafficking properties, were used in an attempt to better understand the structural requirements for the classification of GPCRs. The C-terminus tail of the vasopressin type-2 receptor was added to the ends of D(2)R and D(3)R to increase their affinity to beta-arrestin. A point mutation was introduced into the DRY motif to change their basal activation levels. Among a battery of constructs in which the C-terminus tail and/or DRY motif was altered, class-B behavior was observed with the constructs whose affinities for beta-arrestin were increased complementarily and their signaling was either maintained or regained. In conclusion, the DRY motif and C-terminal tail of the GPCRs determine complementarily their intracellular trafficking behavior by regulating the affinity to beta-arrestin and G protein coupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Arrestins / metabolism*
  • Binding Sites
  • Cell Line
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Kidney / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / physiology*
  • beta-Arrestins

Substances

  • Arrestins
  • Receptors, G-Protein-Coupled
  • beta-Arrestins
  • GTP-Binding Proteins