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蛋白-蛋白间的相互作用可以调控蛋白的表达及其功能。在脑细胞中,胞内蛋白常与膜表面受体的胞内区域结合来调节受体的表达和功能。已有研究表明,G?i/o蛋白偶联的M4受体常受多种结合蛋白的调节。这些结合蛋白通过与受体位于胞浆的区域结合来调节M4受体信号通路的传导效率。钙离子/钙调蛋白依赖的蛋白激酶(Ca2+/calmodulin-dependent protein kinase II,CaMKII)是近年来发现的一种主要密集于突触的蛋白激酶,与M4受体的胞内第二个内环相结合。CaMKII通过磷酸化M4受体来增强M4受体通路对环腺苷酶的抑制作用,进而减少cAMP的合成。在纹状体神经元中,M4受体结合蛋白动态控制M4受体的活性,从而在这些细胞中维持适当的胆碱传导信号通路的活性。可控的胆碱信号通路在维持基底节神经元内胆碱与多巴胺信号的平衡中有至关重要的作用,并由此决定机体对精神兴奋剂引起的多巴胺刺激反应的灵敏度。
Protein-protein interactions regulate the expression and function of proteins. In brain cells, intracellular proteins often bind to the intracellular domain of membrane surface receptors to regulate receptor expression and function. It has been shown that G? I / o protein-coupled M4 receptors are often regulated by a variety of binding proteins. These binding proteins regulate the transduction efficiency of the M4 receptor signaling pathway by binding to the region of the receptor in the cytoplasm. In recent years, Ca2 + / calmodulin-dependent protein kinase II (CaMKII) has been found to be a major concentration of synaptic protein kinase, which interacts with the intracellular second inner loop of M4 receptor Combine. CaMKII enhances the inhibitory effect of the M4 receptor pathway on cyclic adenosine kinase by phosphorylating the M4 receptor, thereby reducing the cAMP synthesis. In striatal neurons, the M4 receptor binding protein dynamically controls the activity of the M4 receptor, thereby maintaining appropriate choline signaling pathways in these cells. The controllable cholinergic signaling pathway plays a crucial role in maintaining the balance of choline and dopamine signals in basal ganglia and thus determines the sensitivity of the body to dopamine-stimulated responses to psychostimulants.