Nie J, Lewis D L
Department of Pharmacology and Toxicology, Medical College of Georgia, Room CB3515, 1120 15th Street, Augusta, GA 30912-2300, USA.
Neuroscience. 2001;107(1):161-7. doi: 10.1016/s0306-4522(01)00335-9.
The human CB1 cannabinoid receptor couples to G(i/o) proteins and inhibits neuronal voltage-gated Ca2+ channels. The role of the C-terminal tail of the CB1 cannabinoid receptor in G(i/o) protein 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 G(i/o) protein 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.
人类CB1大麻素受体与G(i/o)蛋白偶联，并抑制神经元电压门控Ca2+通道。利用颈上神经节神经元表达系统研究了CB1大麻素受体C末端尾巴在G(i/o)蛋白偶联中的作用。缺失远端细胞内C末端尾巴（氨基酸418 - 472）会减慢动力学并降低Ca2+通道抑制的幅度。缺失整个细胞内C末端尾巴（氨基酸401 - 472）则消除了Ca2+通道抑制，表明C末端尾巴近端氨基酸401 - 417在G蛋白信号传导中起关键作用。使用N末端CB1抗体检测了C末端截短受体在细胞表面的表达。两种C末端截短受体均在细胞表面表达，且与野生型CB1大麻素受体无差异。本研究证实，CB1大麻素受体近端细胞内C末端尾巴结构域（氨基酸401 - 417）对G(i/o)蛋白偶联至关重要，而远端C末端尾巴结构域（氨基酸418 - 472）深刻调节信号转导的幅度和动力学。因此，CB1大麻素受体的C末端尾巴在G蛋白偶联中的作用比之前认为的更广泛。
