Cross talk between both pre- and postsynaptic components of glutamatergic neurotransmission plays a crucial role in orchestrating a multitude of brain functions, including synaptic plasticity and motor planning. Metabotropic glutamate receptor (mGluR) 5 exhibits promising therapeutic potential for many neurodevelopmental and neurodegenerative disorders as a consequence of its modulatory control over diverse neuronal networks required for memory, motor coordination, neuronal survival, and differentiation. Given these crucial roles, mGluR5 signaling is under the tight control of glutamate release machinery mediated through vesicular glutamate transporters (VGLUTs) that ultimately dictate glutamatergic output. A particular VGLUT isoform, VGLUT3, exhibits an overlapping, but unique, distribution with mGluR5, and the dynamic cross talk between mGluR5 and VGLUT3 is key for the function of specific neuronal networks involved in motor coordination, emotions, and cognition. Thus, aberrant signaling of the VGLUT3-mGluR5 axis is linked to various pathologies including, but not limited to, Parkinson disease, anxiety disorders, and drug addiction. We argue that a comprehensive profiling of how coordinated VGLUT3-mGluR5 signaling influences overall glutamatergic neurotransmission is warranted.

中文翻译：

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针对囊泡谷氨酸转运蛋白机械：对代谢型谷氨酸受体5信号传导和行为的影响。

谷氨酸能神经传递的突触前和突触后成分之间的串扰在协调多种脑功能（包括突触可塑性和运动计划）中起着至关重要的作用。代谢型谷氨酸受体（mGluR）5由于对记忆，运动协调，神经元存活和分化所需的各种神经元网络的调节控制，对许多神经发育和神经退行性疾病表现出有希望的治疗潜力。考虑到这些关键作用，mGluR5信号传导受最终指示谷氨酸能输出的水泡谷氨酸转运蛋白（VGLUTs）介导的谷氨酸释放机制的严格控制。特定的VGLUT亚型VGLUT3与mGluR5具有重叠但唯一的分布，而mGluR5和VGLUT3之间的动态串扰是参与运动协调，情绪和认知的特定神经元网络功能的关键。因此，VGLUT3-mGluR5轴的异常信号传导与各种病理相关，包括但不限于帕金森氏病，焦虑症和药物成瘾。我们认为，对协调的VGLUT3-mGluR5信号如何影响整体谷氨酸能神经传递的全面分析是必要的。