Role of the fourth intracellular loop of D1-like dopaminergic receptors in conferring subtype-specific signaling properties.
We investigate whether the fourth intracellular loop (IL4) of D1 and D5 dopaminergic receptors (D1R, D5R) confers D1-like subtype-specific signaling properties. Using chimeric receptors (D1R-IL4B and D5R-IL4A), we show that swapping of IL4 leads to a switch in dopamine affinity and constitutive activity of D1R and D5R. Dopamine potency was reduced for both chimeras in comparison with wild-type receptors. Moreover, dopamine-mediated maximal activation was drastically increased in cells expressing D1R-IL4B when compared with those harboring D5R-IL4A or wild-type receptors. In conclusion, IL4 plays a pivotal role in imparting subtype-specific ligand binding and activation properties to highly homologous seven-transmembrane receptors.
Tumova
Katerina
K
Ottawa Health Research Institute, Neuroscience Program, and Departments of Medicine/Cellular and Molecular Medicine/Psychiatry, University of Ottawa, Ottawa, ON, Canada.
Zhang
Dongling
D
Tiberi
Mario
M
D000595:Amino Acid Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011954:Receptors, Dopamine / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D017931:DNA Primers; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4