Mu-opioid receptor heterooligomer formation with the dopamine D1 receptor as directly visualized in living cells.
Our immunohistochemistry experiments demonstrated that the mu-opioid receptor co-localized with the dopamine D1 receptor in neurons of the cortex and caudate nucleus. On the basis of this physiological data we further investigated whether these two G protein coupled receptors formed hetero-oligomers in living cells. To demonstrate hetero-oligomerization we used a novel strategy, the method used harnessed the physiological cellular mechanism for transport of proteins to the nucleus. The nuclear translocation pathway was adapted for the visualization of mu-opioid hetero-oligomers with the dopamine D1 receptor. The receptor hetero-oligomer complex formed resulted in a significantly enhanced surface expression of mu-opioid receptor. This hetero-oligomer formation involved the interaction of mu-opioid receptor with the dopamine D1 receptor carboxyl tail, since a dopamine D1 receptor substituted with the carboxyl of the dopamine D5 receptor failed to increase surface expression of mu-opioid receptor.
Juhasz
Jason R
JR
Department of Pharmacology University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
Hasbi
Ahmed
A
Rashid
Asim J
AJ
So
Christopher H
CH
George
Susan R
SR
O'Dowd
Brian F
BF
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D021381:Protein Transport; D017447:Receptors, Dopamine D1 / Q000737:chemistry / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000378:metabolism*
D017447:Receptors, Dopamine D1; D017450:Receptors, Opioid, mu