Vesicular glutamate transporter isoforms: The essential players in the somatosensory systems
Vesicular glutamate transporter isoforms: The essential players in the somatosensory systems
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DOI：
10.1016/j.pneurobio.2018.09.006
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发表时间：
2018-12
影响因子：
6.7
通讯作者：
Fu-xing Zhang;S. Ge;Yu-Lin Dong;Juan Shi;Yu-Peng Feng;Yang Li-;Yun-Qing Li;Jinlian Li
中科院分区：
文献类型：
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作者：
Fu-xing Zhang;S. Ge;Yu-Lin Dong;Juan Shi;Yu-Peng Feng;Yang Li-;Yun-Qing Li;Jinlian Li
在神经系统中，谷氨酸的传递对于向心传递和不同形式的感觉信号的皮层感知至关重要，这就需要三种同源膜结合蛋白异构体谷氨酸囊泡转运蛋白1-3 （VGLUT - 1）将谷氨酸运送到突触前囊泡中。这些VGLUT1，特别是VGLUT1和VGLUT2，在包括脊髓和三叉神经感觉系统的神经层次的每个中继水平上选择性地标记和定义功能不同的神经元亚群。在这篇综述中，通过仔细研究生物基本层次的每个结构，包括背根/三叉神经节、脊髓背角/三叉神经节感觉核复合体、体感丘脑核和初级体感皮层，我们总结和详细描述了在每个中继中表达不同VGLUT蛋白/转录物亚型的神经元簇，以及它们的区域分布特征（在某些结构中互补分布）。轴突末梢/外周神经支配与生理功能。同样重要的是，VGLUT1/VGLUT2轴突末端在这些结构中的分布模式和特征也得到了概括。最后，一种特殊的VGLUT异构体与其生理作用的相关性，迄今为止主要是通过研究外周受体揭示的，通过参考关于全局和条件VGLUT敲除小鼠的报道来概括。并初步提出了今后研究的方向，如在离子/分子水平上揭示不同VGLUTs在机制和/或药代动力学上的差异，开发基于VGLUTs的止痛药。
In nervous system, glutamate transmission is crucial for centripetal conveyance and cortical perception of sensory signals of different modalities, which necessitates vesicular glutamate transporters 1–3 (VGLUT 1–3), the three homologous membrane-bound protein isoforms, to load glutamate into the presysnaptic vesicles. These VGLUTs, especially VGLUT1 and VGLUT2, selectively label and define functionally distinct neuronal subpopulations at each relay level of the neural hierarchies comprising spinal and trigeminal sensory systems. In this review, by scrutinizing each structure of the organism’s fundamental hierarchies including dorsal root/trigeminal ganglia, spinal dorsal horn/trigeminal sensory nuclear complex, somatosensory thalamic nuclei and primary somatosensory cortex, we summarize and characterize in detail within each relay the neuronal clusters expressing distinct VGLUT protein/transcript isoforms, with respect to their regional distribution features (complementary distribution in some structures), axonal terminations/peripheral innervations and physiological functions. Equally important, the distribution pattern and characteristics of VGLUT1/VGLUT2 axon terminals within these structures are also epitomized. Finally, the correlation of a particular VGLUT isoform and its physiological role, disclosed thus far largely via studying the peripheral receptors, is generalized by referring to reports on global and conditioned VGLUT-knockout mice. Also, researches on VGLUTs relating to future direction are tentatively proposed, such as unveiling the elusive differences between distinct VGLUTs in mechanism and/or pharmacokinetics at ionic/molecular level, and developing VGLUT-based pain killers.