title: Two amino acids in each of D1 and D2 dopamine receptor cytoplasmic regions are involved in D1-D2 heteromer formation.
abstract: D(1) and D(2) dopamine receptors exist as heteromers in cells and brain tissue and are dynamically regulated and separated by agonist concentrations at the cell surface. We determined that these receptor pairs interact primarily through discrete amino acids in the cytoplasmic regions of each receptor, with no evidence of any D(1)-D(2) receptor transmembrane interaction found. Specifically involved in heteromer formation we identified, in intracellular loop 3 of the D(2) receptor, two adjacent arginine residues. Substitution of one of the arginine pair prevented heteromer formation. Also involved in heteromer formation we identified, in the carboxyl tail of the D(1) receptor, two adjacent glutamic acid residues. Substitution of one of the glutamic acid pair prevented heteromer formation. These amino acid pairs in D(1) and D(2) receptors are oppositely charged, and presumably interact directly by electrostatic interactions.
authors.affiliation: Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. brian.odowd@utoronto.ca
authors.forename: Brian F
authors.initials: BF
authors.lastname: O'Dowd
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ji
authors.forename: Tuan
authors.initials: T
authors.lastname: Nguyen
authors.forename: Susan R
authors.initials: SR
authors.lastname: George
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001120:Arginine / Q000737:chemistry* / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017447:Receptors, Dopamine D1 / Q000737:chemistry* / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000235:genetics
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001120:Arginine
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