Volume-regulated anion channel--a frenemy within the brain.
Volume-regulated anion channel--a frenemy within the brain.
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DOI：
10.1007/s00424-015-1765-6
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Mongin AA
中科院分区：
文献类型：
--
作者：
Mongin AA
容量调节阴离子通道（VRAC）是氯离子/阴离子通道超家族中一个广泛表达但又高度神秘的成员。它被细胞肿胀激活，并介导大多数脊椎动物细胞（包括中枢神经系统（CNS）细胞）中调节性细胞体积减少。在脑中，除了其在细胞体积调节中的关键作用外，VRAC被认为在细胞增殖、凋亡、迁移和生理活性分子的释放中起作用。虽然这些作用并不局限于CNS，但VRAC在大脑中的相对重要性被其生理学的几个独特方面放大。一个重要的例子是VRAC对兴奋性氨基酸神经递质谷氨酸和天冬氨酸的释放的贡献。后一个过程被认为对正常脑功能（如星形胶质细胞-神经元信号传导）和神经病理学（通过促进中风和创伤性脑损伤中神经元细胞的兴奋性毒性死亡）都有影响。尽管在该领域的许多工作，VRAC的分子性质仍然未知，直到不到两年前。两篇先驱出版物将VRAC鉴定为由富含亮氨酸的含重复序列8（LRRC 8）蛋白形成的异源六聚体。这些发现激发了该领域的研究，并可能导致我们对VRAC在大脑以及其他器官和组织中的位置和作用的理解发生巨大变化。本综述简要概括了中枢神经系统中的关键发现，并侧重于LRRC 8发现对神经科学研究进一步进展的预期影响。
Volume regulated anion channel (VRAC) is a ubiquitously expressed yet highly enigmatic member of the superfamily of chloride/anion channels. It is activated by cellular swelling and mediates regulatory cell volume decrease in a majority of vertebrate cells, including those in the central nervous system (CNS). In the brain, besides its crucial role in cellular volume regulation, VRAC is thought to play a part in cell proliferation, apoptosis, migration, and release of physiologically active molecules. Although these roles are not exclusive to the CNS, the relative significance of VRAC in the brain is amplified by several unique aspects of its physiology. One important example is contribution of VRAC to release of the excitatory amino acid neurotransmitters, glutamate and aspartate. This latter process is thought to have impact on both normal brain functioning (such as astrocyte-neuron signaling) and neuropathology (via promoting the excitotoxic death of neuronal cells in stroke and traumatic brain injury). In spite of much work in the field the molecular nature of VRAC remained unknown until less than two years ago. Two pioneer publications identified VRAC as the hetero-hexamer formed by the leucine-rich repeat-containing 8 (LRRC8) proteins. These findings galvanized the field and are likely to result in dramatic revisions to our understanding of the place and role of VRAC in the brain, as well as other organs and tissues. The present review briefly recapitulates critical findings in the CNS, and focuses on anticipated impact on the LRRC8 discovery on further progress in neuroscience research.
影响因子：
3.8
作者：
Sarkadi, B;Mack, E;Rothstein, A
通讯作者：
Rothstein, A
影响因子：
3.8
作者：
Sarkadi, B;Mack, E;Rothstein, A
通讯作者：
Rothstein, A