Analysis of the molecular mechanisms of formation and trafficking to the cell surface of the G protein-coupled receptors that require accessory proteins for their expression.

γ-氨基丁酸（GABA）被认为是中枢和周围神经系统的一种抑制性神经递质。GABA受体分为两种类型，一种属于离子型受体（GABA_A和GABA_C），另一种属于代谢性g蛋白偶联受体（GABA_B）。GABA_B受体于1997年被克隆为GABA_<B1>受体，此后，许多工作都集中在克隆的GABA_B受体的异源功能表达上。然而，没有一项表达研究成功。因此，表达研究的失败提示存在GABA_B受体功能表达的额外蛋白。现在已知功能GABA_B受体需要与GABA_<B1>和GBA_<B2>受体形成异源二聚体。在目前的研究中，我们重点研究了GABA_B受体是如何作为异源二聚体构建的，以及受体是如何通过多种检测系统运输到细胞膜上的。我们发现功能性GABA_B受体在转运到细胞膜之前已经形成。我们还发现GABA_<B1>受体是其配体结合所必需的，而GABA_<B2>受体是其通过异质G蛋白进行细胞内信号传递所必需的。我们的研究仍在进行中，希望能继续阐明GABA_B受体的形成机制，以及GABA_B受体为何需要异聚体才能实现其功能表达。

γ-Amino butyric acids (GABA) is known to act as an inhibitory neurotransmitter on the central and peripheral nervous system. Receptors for GABA are divided into two types : one belongs to ionotropic receptors (GABA_A and GABA_C) and another belongs to metabotoropic G-protein coupled receptors (GABA_B). GABA_B receptor has been cloned in 1997 as a GABA_<B1> receptor and since then, many of works have been focused on the heterologous functional expression of the cloned GABA_B receptors. However, none of the expression study has succeeded. Accordingly the failure of the expression study suggested us the existence of some additional protein(s) for the functional expression of GABA_B receptors. Now functional GABA_B receptors are known to be required to be formed heterodimer with GABA_<B1> and GBA_<B2> receptors.In the present study we focused on how functional GABA_B receptors are constructed as heterodimer and how the receptors are trafficked to the cell membrane, by the use of multiple assay systems. We found that functional GABA_B receptors are already formed before trafficked to cell membranes. We also found that GABA_<B1> receptors are required for their ligand binding while GABA_<B2> receptors are indispensable for their intracellular signaling through heteromeric G proteins.We are still in progress of our study and hope to continue to clarify the mechanism how GABA_B receptors are formed and why GABA_B receptors are required to be heteromultimer for their functional expression.