Role of electrostatic interaction in receptor-receptor heteromerization

Amina S. Woods, Francisco Ciruela, Kjell Fuxe, Luigi F. Agnati, Carmen Lluis, Rafael Franco, Sergi Ferré

Research output: Contribution to journalArticlepeer-review

Abstract

Using pull-down and mass spectrometry experiments, we have previously demonstrated that adenosine A2A-dopamine D2 receptor-receptor heteromerization depends on an electrostatic interaction between an Arg-rich epitope from the third intracellular loop of the D 2 receptor (217RRRRKR222) and two adjacent Asp residues (DD401-402) or a phosphorylated Ser (pS374) residue in the carboxyl terminus of the A2A receptor. It has been demonstrated recently that a specific region in the carboxyl terminus of the dopamine D1 receptor (L387-L416) and a specific region in the carboxyl terminus of the NR1-1 subunit of the NMDA receptor (E834-S938) are involved in D1-NMDA receptor-receptor heteromerization. Careful perusal of these interacting regions shows the presence of a phosphorylated serine (pS397) and adjacent glutamates (EE404-405) in the D1 receptor, whereas NR1-1 contains three adjacent Arg residues (RRR893-896). These epitopes are highly conserved in all species, a sign that the epitopes are likely to be involved in a physiologically significant activity. If similar epitopes are found to be involved in the formation of receptor heteromers other than A 2A-D2 and D1-NMDA, the epitope-epitope electrostatic interaction might represent an important general mechanism underlying receptor-receptor interactions.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalJournal of Molecular Neuroscience
Volume26
Issue number2-3
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Dopamine D
  • Electrostatic interaction
  • Heteromers
  • Mass spectrometry
  • NMDA receptor
  • Receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

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