title: Dopamine D2 and D4 receptor heteromerization and its allosteric receptor-receptor interactions.
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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van Craenenbroeck
authors.forename: Wilber
authors.initials: W
authors.lastname: Romero-Fernandez
authors.forename: Diego
authors.initials: D
authors.lastname: Guidolin
authors.forename: Amina S
authors.initials: AS
authors.lastname: Woods
authors.forename: Alicia
authors.initials: A
authors.lastname: Rivera
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Tarakanov
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D002460:Cell Line; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D055503:Protein Multimerization; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000737:chemistry* / Q000235:genetics
chemical_list: D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3