Characterization of the desensitization properties of five dopamine receptor subtypes and alternatively spliced variants of dopamine D2 and D4 receptors
Characterization of the desensitization properties of five dopamine receptor subtypes and alternatively spliced variants of dopamine D2 and D4 receptors
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DOI：
10.1016/j.bbrc.2006.09.090
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发表时间：
2006-11-24
影响因子：
3.1
通讯作者：
Kim, Kyeong-Man
中科院分区：
文献类型：
--
作者：
Cho, Dong-Im;Beorn, SunRyeo;Kim, Kyeong-Man
大脑多巴胺能活动的适当调节对于维持正常的心理功能至关重要。在这项研究中，检查了五种不同多巴胺受体亚型以及多巴胺 D-2 和 D-4 的选择性剪接变体的调节特性。 D1R、D2R、D5R 的刺激而非 D3R、D4R 的刺激导致 P-抑制蛋白强烈易位至质膜。当D1R或D3R与D2R共表达时，D1R显着抑制D2R的隔离，这表明D1R对D2R隔离的抑制作用可以解释两种受体之间的协同活性。 D2R 选择性剪接异构体的隔离受到 GRK 和 β-arrestins 的不同调节。 D4R 的三种选择性剪接变体产生了相似水平的 P-抑制蛋白易位，并且对第三细胞质环内的 D4R 缺失突变体的研究表明，包含 SH3 结合结构域的区域负责 β-抑制蛋白易位。 (c) 2006 Elsevier Inc. 保留所有权利。
Proper regulation of brain dopaminergic activity is essential for maintaining normal mental functions. In this study, the regulatory properties of five different dopamine receptor subtypes and alternative splicing variants of dopamine D-2 and D-4 were examined. The stimulation of D1R, D2R, D5R but not D3R, D4R caused the robust translocation of P-arrestin to the plasma membrane. When D1R or D3R were co-expressed with D2R, D1R significantly inhibited the sequestration of D2R, suggesting that the inhibitory effects of D1R on the D2R sequestration could explain the synergistic activity between two receptors. The sequestration of alternatively spliced isoforms of D2R was differently regulated by GRKs and beta-arrestins. Three alternative splicing variants of D4R produced a similar level of P-arrestin translocation, and the studies with the deletion mutants of D4R within the third cytoplasmic loop revealed that the regions containing the SH3-binding domains are responsible for the beta-arrestin translocation. (c) 2006 Elsevier Inc. All rights reserved.