Distinct function of the cytoplasmic tail in human D1‐like receptor ligand binding and coupling

FEBS Letters

Jackson, Adele¹  Iwasiow, Rafal M.¹  Tiberi, Mario¹ 

[1] Neurosciences, Loeb Health Research Institute, Ottawa Hospital (Civic Campus) and Department of Cellular and Molecular Medicine, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ont. K1Y 4K9, Canada

关键词: G protein-coupled receptor;    Constitutive activity;    Dopamine;    D1-like receptor;    Binding affinity;    G protein activation;    GPCR;    G protein-coupled receptor;    EL3;    third extracellular loop;    TRL;    terminal receptor locus;    IBMX;    1-methyl-3-isobutylxanthine;   

DOI  :  10.1016/S0014-5793(00)01315-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown