Inhibition of cell surface expression by mutant receptors demonstrates that D2 dopamine receptors exist as oligomers in the cell.
Numerous mutant G protein-coupled receptors with diminished or no function have been described that are naturally occurring or that are the product of gene manipulation. It has largely been assumed that receptor mutants do not affect the function of the wild-type receptor; however, the occurrence of G protein-coupled receptor dimerization suggests the possibility that an intermolecular interaction between mutant and wild-type receptors can occur. We have shown previously that the D2 dopamine receptor (D2DR) exists as dimers in cell lines and brain tissue. In this study, we demonstrated that mutant D2DR can modulate the function of the wild-type D2DR. While attempting to elucidate the structure of the D2DR dimer, we demonstrated that nonfunctional D2DR substitution and truncation mutants antagonized wild-type D2DR function. Furthermore, from analyses of this interaction between the receptor mutants and the D2DR, using photoaffinity labeling, we provide evidence that the D2DR is oligomeric in the cell.
Lee
S P
SP
Department of Pharmacology, University of Toronto, Ontario, Canada.
O'Dowd
B F
BF
Ng
G Y
GY
Varghese
G
G
Akil
H
H
Mansour
A
A
Nguyen
T
T
George
S R
SR
D019943:Amino Acid Substitution; D000818:Animals; D001704:Biopolymers; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D019281:Dimerization; D017353:Gene Deletion; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014162:Transfection
D001704:Biopolymers; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D017448:Receptors, Dopamine D2