Distinct function of the cytoplasmic tail in human D1-like receptor ligand binding and coupling |
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Authors: | Jackson A Iwasiow R M Tiberi M |
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Institution: | Neurosciences, Loeb Health Research Institute, Ottawa Hospital (Civic Campus) and Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada. |
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Abstract: | To delineate the role of the cytoplasmic tail in the distinct binding and coupling properties of human dopamine D1-like receptors, chimeric receptors were generated in which the entire tail region of wild-type human D1A (or D1) and D1B (or D5) receptors was exchanged. The hD1A-D1BT, but not hD1B-D1AT, receptor expression was dramatically reduced compared with wild-type receptor expression. Swapping the cytoplasmic tail resulted in a full switch of dopamine binding affinity and constitutive activity, while dopamine potency decreased and agonist-mediated maximal activation of adenylyl cyclase increased for both chimeras. Hence, the cytoplasmic tail plays a crucial role in D1-like receptor expression, agonist binding affinity and constitutive activation but regulates in a distinct fashion the formation of D1A and D1B receptor active states upon dopamine binding. |
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