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

Dasiel O. Borroto-Escuela, Kathleen Van Craenenbroeck, Wilber Romero-Fernandez, Diego Guidolin, Amina S. Woods, Alicia Rivera, Guy Haegeman, Luigi F. Agnati, Alexander O. Tarakanov, Kjell Fuxe

Research output: Contribution to journalArticlepeer-review

Abstract

Dopamine D2 and D4 receptors partially codistribute in the dorsal striatum and appear to play a fundamental role in complex behaviors and motor function. The discovery of D2R-D4.xR (D4.2R, D4.4R or D4.7R) heteromers has been made in cellular models using co-immunoprecipitation, in situ Proximity Ligation Assays and BRET1 techniques with the D2R and D4.7R receptors being the least effective in forming heteromers. Allosteric receptor-receptor interactions in D2R-D4.2R and D2R-D4.4 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.

Original languageEnglish (US)
Pages (from-to)928-934
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume404
Issue number4
DOIs
StatePublished - Jan 28 2011

Keywords

  • Allosteric modulation
  • Dopamine DR receptor
  • Dopamine DR receptor
  • G protein-coupled receptors
  • Heteromerization
  • Protein-protein interactions.

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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