PDF(Pubmed)
Abstract：
Bioluminescence and fluorescence resonance energy transfer (BRET and FRET) together with the proximity ligation method revealed the existence of G-protein-coupled receptors, Ionotropic and Receptor tyrosine kinase heterocomplexes, e.g., A2AR-D2R, GABAA-D5R, and FGFR1-5-HT1AR heterocomplexes. Molecular integration takes place through allosteric receptor-receptor interactions in heteroreceptor complexes of synaptic and extra-synaptic regions. It involves the modulation of receptor protomer recognition, signaling and trafficking, as well as the modulation of behavioral responses. Allosteric receptor-receptor interactions in hetero-complexes give rise to concepts like meta-modulation and protein modulation. The introduction of receptor-receptor interactions was the origin of the concept of meta-modulation provided by Katz and Edwards in 1999, which stood for the fine-tuning or modulation of nerve cell transmission. In 2000-2010, Ribeiro and Sebastiao, based on a series of papers, provided strong support for their view that adenosine can meta-modulate (fine-tune) synaptic transmission through adenosine receptors. However, another term should also be considered: protein modulation, which is the key feature of allosteric receptor-receptor interactions leading to learning and consolidation by novel adapter proteins to memory. Finally, it must be underlined that allosteric receptor-receptor interactions and their involvement both in brain disease and its treatment are of high interest. Their pathophysiological relevance has been obtained, especially for major depressive disorder, cocaine use disorder, and Parkinson\'s disease.
摘要：
生物发光和荧光共振能量转移（BRET和FRET）以及邻近连接方法揭示了G蛋白偶联受体的存在，离子型和受体酪氨酸激酶异型复合物，例如，A2AR-D2R,GABAA-D5R,和FGFR1-5-HT1AR杂复合物。分子整合通过突触和突触外区域的异受体复合物中的变构受体-受体相互作用发生。它涉及受体前体识别的调制，信号和贩运，以及行为反应的调节。异质复合物中的变构受体-受体相互作用产生了诸如元调节和蛋白质调节的概念。受体-受体相互作用的引入是Katz和Edwards于1999年提供的元调节概念的起源，该概念代表神经细胞传递的微调或调节。2000-2010年，里贝罗和塞巴斯蒂安，基于一系列的论文,为他们的观点提供了强有力的支持，即腺苷可以通过腺苷受体调节（微调）突触传递。然而,另一个术语也应该被考虑：蛋白质调制，这是变构受体-受体相互作用的关键特征，导致新型衔接蛋白对记忆的学习和巩固。最后,必须强调的是，变构受体-受体相互作用及其在脑疾病及其治疗中的参与是非常感兴趣的。已经获得了它们的病理生理相关性，尤其是重度抑郁症,可卡因使用障碍,和帕金森病。
