Perez-Mansilla Borja, Nurrish Stephen
MRC Cell Biology Unit, MRC Laboratory for Molecular Cell Biology and Department of Neurobiology, Physiology and Pharmacology, University College London, London, United Kingdom.
Adv Genet. 2009;65:145-192. doi: 10.1016/S0065-2660(09)65004-5.
The Caenorhabditis elegans neuromuscular junction (NMJ) is one of the best studied synapses in any organism. A variety of genetic screens have identified genes required both for the essential steps of neurotransmitter release from motorneurons as well as the signaling pathways that regulate rates of neurotransmitter release. A number of these regulatory genes encode proteins that converge to regulate neurotransmitter release. In other cases genes are known to regulate signaling at the NMJ but how they act remains unknown. Many of the proteins that regulate activity at the NMJ participate in a network of heterotrimeric G-protein signaling pathways controlling the release of synaptic vesicles and/or dense-core vesicles (DCVs). At least four heterotrimeric G-proteins (Galphaq, Galpha12, Galphao, and Galphas) act within the motorneurons to control the activity of the NMJ. The Galphaq, Galpha12, and Galphao pathways converge to control production and destruction of the lipid-bound second messenger diacylglycerol (DAG) at sites of neurotransmitter release. DAG acts via at least two effectors, MUNC13 and PKC, to control the release of both neurotransmitters and neuropeptides from motorneurons. The Galphas pathway converges with the other three heterotrimeric G-protein pathways downstream of DAG to regulate neuropeptide release. Released neurotransmitters and neuropeptides then act to control contraction of the body-wall muscles to control locomotion. The lipids and proteins involved in these networks are conserved between C. elegans and mammals. Thus, the C. elegans NMJ acts as a model synapse to understand how neuronal activity in the human brain is regulated.
秀丽隐杆线虫的神经肌肉接头（NMJ）是所有生物体中研究最为深入的突触之一。多种遗传筛选已鉴定出运动神经元释放神经递质的关键步骤以及调节神经递质释放速率的信号通路所需的基因。其中许多调节基因编码的蛋白质共同作用来调节神经递质的释放。在其他情况下，已知一些基因可调节NMJ处的信号传导，但它们的作用方式仍不清楚。许多调节NMJ活性的蛋白质参与了异源三聚体G蛋白信号通路网络，该网络控制突触小泡和/或致密核心小泡（DCV）的释放。至少四种异源三聚体G蛋白（Gαq、Gα12、Gαo和Gαs）在运动神经元内起作用，以控制NMJ的活性。Gαq、Gα12和Gαo信号通路共同作用，在神经递质释放位点控制脂质结合的第二信使二酰基甘油（DAG）的产生和降解。DAG通过至少两种效应器MUNC13和PKC起作用，以控制运动神经元释放神经递质和神经肽。Gαs信号通路在DAG下游与其他三种异源三聚体G蛋白信号通路汇聚，以调节神经肽的释放。释放的神经递质和神经肽随后作用于控制体壁肌肉的收缩，从而控制运动。这些网络中涉及的脂质和蛋白质在秀丽隐杆线虫和哺乳动物之间是保守的。因此，秀丽隐杆线虫的NMJ可作为一个模型突触，用于理解人类大脑中的神经元活动是如何被调节的。
