Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600; Department of Anatomy and Cell Biology, University of Illinois, Chicago, Illinois 60612-7308.
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600.
J Biol Chem. 2019 Feb 1;294(5):1661-1670. doi: 10.1074/jbc.TM118.004163.
Throughout the past five decades, tremendous advancements have been made in our understanding of G protein signaling and presynaptic inhibition, many of which were published in the under the tenure of Herb Tabor as Editor-in-Chief. Here, we identify these critical advances, including the formulation of the ternary complex model of G protein-coupled receptor signaling and the discovery of Gβγ as a critical signaling component of the heterotrimeric G protein, along with the nature of presynaptic inhibition and its physiological role. We provide an overview for the discovery and physiological relevance of the two known Gβγ-mediated mechanisms for presynaptic inhibition: first, the action of Gβγ on voltage-gated calcium channels to inhibit calcium influx to the presynaptic active zone and, second, the direct binding of Gβγ to the SNARE complex to displace synaptotagmin downstream of calcium entry, which has been demonstrated to be important in neurons and secretory cells. These two mechanisms act in tandem with each other in a synergistic manner to provide more complete spatiotemporal control over neurotransmitter release.
在过去的五十年中，我们对 G 蛋白信号转导和突触前抑制的理解取得了巨大的进展，其中许多进展都是在 Herb Tabor 担任主编期间在 上发表的。在这里，我们确定了这些关键的进展，包括 G 蛋白偶联受体信号转导的三元复合物模型的提出，以及 Gβγ 作为异三聚体 G 蛋白的关键信号成分的发现，以及突触前抑制的性质及其生理作用。我们提供了对两种已知的 Gβγ 介导的突触前抑制机制的发现和生理相关性的概述：首先，Gβγ 对电压门控钙通道的作用，以抑制钙流入突触前活性区，其次，Gβγ 与 SNARE 复合物的直接结合，以置换钙内流下游的突触结合蛋白，这已被证明在神经元和分泌细胞中很重要。这两种机制协同作用，以协同的方式提供对神经递质释放更完整的时空控制。
