The proximal and distal C-terminal tail domains of the CB1 cannabinoid receptor mediate G protein coupling.
The proximal and distal C-terminal tail domains of the CB1 cannabinoid receptor mediate G protein coupling.
复制标题
CB1 大麻素受体的近端和远端 C 端尾部结构域介导 G 蛋白偶联。
DOI：
10.1016/s0306-4522(01)00335-9
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发表时间：
2001
期刊：
影响因子：
3.3
通讯作者：
Lewis,DL
中科院分区：
文献类型：
--
作者：
Nie,J;Lewis,DL
人CB 1大麻素受体与Gi/o蛋白偶联并抑制神经元电压门控Ca 2+通道。使用上级颈神经节神经元表达系统检查了CB 1大麻素受体的C-末端尾在Gi/o蛋白偶联中的作用。远端细胞内C-末端尾（氨基酸418-472）的缺失减缓了动力学，并降低了Ca 2+通道抑制的幅度。整个细胞内C-末端尾（氨基酸401-472）的缺失消除了Ca 2+通道抑制，证明了C-末端尾的近端氨基酸401-417在G蛋白信号传导中的关键作用。使用N-末端CB 1抗体检测细胞表面上C-末端截短受体的表达。这两种C-末端截短的受体都在细胞表面上表达，并且与野生型CB 1大麻素受体没有区别。本研究确定了近端CB 1大麻素受体细胞内C-末端尾结构域（氨基酸401-417）对于Gi/o蛋白偶联是关键的，并且远端C-末端尾结构域（氨基酸418-472）深刻地调节信号转导的幅度和动力学。因此，CB 1大麻素受体的C-末端尾部在G蛋白偶联中的作用比以前认为的更广泛。
The human CB1 cannabinoid receptor couples to Gi/oproteins and inhibits neuronal voltage-gated Ca2+channels. The role of the C-terminal tail of the CB1 cannabinoid receptor in Gi/oprotein coupling was examined using the superior cervical ganglion neuronal expression system. Deletion of the distal intracellular C-terminal tail (amino acids 418–472) slowed the kinetics and reduced the magnitude of Ca2+channel inhibition. Deletion of the entire intracellular C-terminal tail (amino acids 401–472) abolished Ca2+channel inhibition demonstrating the critical role of the proximal amino acids 401–417 of the C-terminal tail in G protein signaling. Expression of the C-terminal truncated receptors on the cell surface was examined using an N-terminal CB1 antibody. Both the C-terminal truncated receptors were expressed on the cell surface and were no different from wild type CB1 cannabinoid receptors. This study establishes that the proximal CB1 cannabinoid receptor intracellular C-terminal tail domain (amino acids 401–417) is critical for Gi/oprotein coupling and that the distal C-terminal tail domain (amino acids 418–472) profoundly modulates both the magnitude and kinetics of signal transduction. Thus, the C-terminal tail of the CB1 cannabinoid receptor has a wider role in G protein coupling than was previously thought.