Neuman I, Solano A R, Paz C, Mele P, Cornejo Maciel F, Lemos J R, Fernandez H N, Podesta E J
Department of Biochemistry, School of Medicine, University of Buenos Aires, Argentina.
J Steroid Biochem Mol Biol. 1991;40(1-3):441-51. doi: 10.1016/0960-0760(91)90214-p.
Luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) receptors are coupled to intracellular effector systems, most notably adenylate cyclase, through guanyl nucleotide-binding proteins or G-proteins. The molecular mechanism involved in the dynamic coupling of the LH/hCG receptor however, are not known. It has been postulated that receptor aggregation at the molecular level plays a critical role in this process. There have been attempts to understand the receptor association and dissociation phenomena at the molecular level. One of them involves the participation of the major histocompatibility complex (MHC) class I antigen in the mechanism of receptor activation and/or expression. One molecular basis for these mechanisms consists of a physical interaction between MHC proteins and receptors to form "compound receptors" able to transfer a hormonal signal to the cell. Using a photo-reactive probe we demonstrated that the LH/hCG receptors and the class I antigens are closely associated in the membrane. Thus, it is possible to form covalent complexes of hCG and class I antigens through the binding of the hormone to specific receptors. These findings imply that LH/hCG receptors and the MHC class I antigens may interact at the level of the plasma membrane in the mechanism of LH action. We also performed experiments using a single cell and limiting stimulation to a patch of membrane. The results stimulating the cell in a localized area suggested that even if all components are entirely free to float there is a constraint in the localization of the receptor, G-protein, and/or the effector, supporting the constraint dissociation model. Within a limited area subunits could dissociate, but they would not be free to diffuse throughout the membrane. Moreover the concept of compartmentalization that has been utilized to explain some inconsistencies in second-messenger action now can be proved by experimental design.
促黄体生成素（LH）和人绒毛膜促性腺激素（hCG）受体通过鸟苷酸结合蛋白或G蛋白与细胞内效应系统偶联，最显著的是腺苷酸环化酶。然而，LH/hCG受体动态偶联所涉及的分子机制尚不清楚。据推测，分子水平上的受体聚集在这一过程中起关键作用。人们曾试图在分子水平上理解受体的缔合和解离现象。其中之一涉及主要组织相容性复合体（MHC）I类抗原参与受体激活和/或表达的机制。这些机制的一个分子基础是MHC蛋白与受体之间的物理相互作用，以形成能够将激素信号传递给细胞的“复合受体”。我们使用光反应探针证明，LH/hCG受体与I类抗原在膜中紧密相关。因此，通过激素与特定受体的结合，有可能形成hCG与I类抗原的共价复合物。这些发现意味着，在LH作用机制中，LH/hCG受体与MHC I类抗原可能在质膜水平上相互作用。我们还使用单细胞进行实验，并将刺激限制在一小片膜上。在局部区域刺激细胞的结果表明，即使所有成分完全可以自由漂浮，受体、G蛋白和/或效应器的定位仍存在限制，这支持了限制解离模型。在有限的区域内，亚基可以解离，但它们不会自由扩散到整个膜中。此外，用于解释第二信使作用中一些不一致现象的区室化概念现在可以通过实验设计得到证明。
