Identification and analysis of factors that regulate cell surface expression of G-protein coupled receptor

氨基丁酸(γ-氨基丁酸)是中枢和外周神经系统的抑制性神经递质。GABA受体分为两类：一类是离子亲和型受体(GABA_A和GABA_C)，另一类是代谢型G蛋白偶联受体(GABA_B)。GABA_B受体作为一种GABA_B受体于1997年被克隆，此后人们对克隆的GABA_B受体的异源功能表达进行了大量研究。然而，没有一项表达研究取得成功。因此，表达研究的失败提示我们存在一些额外的蛋白质(S)来实现GABAB受体的功能表达。我们以前已经报道过，功能性的GABA_B受体实际上是在非洲爪哇的卵母细胞中表达的，表达大鼠脑的Poly(A)^+RNA，其中丰富地表达了GABA_B受体(Uezono等，Biochem)。生物群落。[中英文摘要]Re.Commun.241：476-(1997)；Uezono等人，神经报告9：583-(1998))。W…因此，更多的人决定用同时表达大鼠聚(A)+RNA和克隆的GABA_B受体的卵母细胞克隆GABAB受体表达因子(S)。在这样的实验过程中，其他人在1998年底证明了GABA_B受体的异构化是GABAB受体功能表达所必需的。因此，我们改变了主意，用克隆的GABA_B受体异构化来研究GABAB受体如何发挥作用的机制。和GABA_1、B_2、G_2受体。与此同时，另一类代谢性受体肾上腺髓质素受体被发现与降钙素受体样受体(CRLR)和称为受体活性修饰蛋白(RAMPS)的小蛋白形成复合体发挥作用。然后我们利用肾上腺髓质素受体(CRLR和RAMPS)，比较了肾上腺髓质素受体的形成机制和GABA_B受体的形成机制。我们的研究仍在进行中，希望继续澄清GABA_B受体的形成机制，以及为什么需要GABA_B受体作为异构体，因为它们的功能表达较少

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, a lot of works have been focused on the heterologous functional expression of the cloned GABA_B receptors. However, none of the expression study has succeeded. Accodingly the failure of the expression study suggested us the existence of some additional protein (s) for the functional expression of GABA_B receptors. We have previously reported that functional GABA_B receptors are actually expressed in Xenopus oocytes expressing the rat brain poly(A)^+ RNA which abundantly express the GABA_B receptor (Uezono et al., Biochem. Biophys. Res. Commun. 241 : 476- (1997) ; Uezono et al., NeuroReport 9 : 583- (1998)). W … More e therefore determined to clone the 'GABA_B receptor expressing factor (s)' with the oocytes expressing both the rat poly(A)^+ RNA and cloned GABA_<B1> receptor.In the course of such experiments, others have demonstrated in late 1998 that heteromultimerization of GABA_<B1> and newly cloned GABA_<B2> receptors are required for functional expression of GABA_B receptors.So we have changed our mind to investigate the mechanism of how GABA_B receptors are required heteromultimerization to be functional, with the cloned GABA_<B2> and GABA_<B2> receptors. In the mean time, another type of metabotoropic receptor namely adrenomedullin receptor is found to form complex with calcitonin receptor-like receptor (CRLR) and small proteins called 'receptor-activity-modifying proteins (RAMPs)' to be functional. We then took advantage of adrenomedullin receptors (CRLR and RAMPs) and compared the mechanism of adrenomedullin receptor formation with that of GABA_B receptor formation.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 Less