Dopamine D2 and D4 receptor heteromerization and its allosteric receptor-receptor interactions

Biochem Biophys Res Commun. 2011 Jan 28;404(4):928-34. doi: 10.1016/j.bbrc.2010.12.083. Epub 2010 Dec 22.

Abstract

Dopamine D(2) and D(4) receptors partially codistribute in the dorsal striatum and appear to play a fundamental role in complex behaviors and motor function. The discovery of D(2)R-D(4.)(x)R (D(4.2)R, D(4.4)R or D(4.7)R) heteromers has been made in cellular models using co-immunoprecipitation, in situ Proximity Ligation Assays and BRET(1) techniques with the D(2)R and D(4.7)R receptors being the least effective in forming heteromers. Allosteric receptor-receptor interactions in D(2)R-D(4.2)R and D(2)R-D(4.4) R heteromers were observed using the MAPK assays indicating the existence of an enhancing allosteric receptor-receptor interaction in the corresponding heteromers between the two orthosteric binding sites. The bioinformatic predictions suggest the existence of a basic set of common triplets (ALQ and LRA) in the two participating receptors that may contribute to the receptor-receptor interaction interfaces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Cell Line
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Conformation
  • Protein Multimerization
  • Receptors, Dopamine D2 / chemistry*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D4 / chemistry*
  • Receptors, Dopamine D4 / genetics

Substances

  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3