Mu-opioid receptor heterooligomer formation with the dopamine D 1 receptor as directly visualized in living cells

• Published in: European journal of pharmacology Vol. 581; no. 3; pp. 235 - 243
• Main Authors: Juhasz, Jason R., Hasbi, Ahmed, Rashid, Asim J., So, Christopher H., George, Susan R., O'Dowd, Brian F.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2008
• Subjects: Cell surface expression; Dopamine D 1 receptors; Hetero-oligomerization; Mu-opioid receptors; Nuclear localization signal; BRET; GFP; Hetero-oligomerization; NLS; DAMGO; Dopamine D 1 receptors; Cell surface expression; Nuclear localization signal; RFP; Mu-opioid receptors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.11.060

Our immunohistochemistry experiments demonstrated that the mu-opioid receptor co-localized with the dopamine D 1 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 D 1 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 D 1 receptor carboxyl tail, since a dopamine D 1 receptor substituted with the carboxyl of the dopamine D 5 receptor failed to increase surface expression of mu-opioid receptor.