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锌转运蛋白 3(ZnT3)与中枢神经系统功能中的囊泡锌

Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function.

机构信息

Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.

出版信息

Neurosci Biobehav Rev. 2017 Sep;80:329-350. doi: 10.1016/j.neubiorev.2017.06.006. Epub 2017 Jun 15.

Abstract

Zinc transporter 3 (ZnT3) is the sole mechanism responsible for concentrating zinc ions within synaptic vesicles in a subset of the brain's glutamatergic neurons. This vesicular zinc can then be released into the synaptic cleft in an activity-dependent fashion, where it can exert many signaling functions. This review provides a comprehensive discussion of the localization and function of ZnT3 and vesicular zinc in the central nervous system. We begin by reviewing the fundamentals of zinc homeostasis and transport, and the discovery of ZnT3. We then focus on four main topics. I) The anatomy of the zincergic system, including its development and its modulation through experience-dependent plasticity. II) The role of zinc in intracellular signaling, with a focus on how zinc affects neurotransmitter receptors and synaptic plasticity. III) The behavioural characterization of the ZnT3 KO mouse, which lacks ZnT3 and, therefore, vesicular zinc. IV) The roles of ZnT3 and vesicular zinc in health and disease.

摘要

锌转运蛋白 3(ZnT3)是唯一负责在大脑中谷氨酸能神经元的一部分中使锌离子在突触小泡内浓缩的机制。这种囊泡内的锌可以以活动依赖性的方式释放到突触间隙中,在那里它可以发挥许多信号功能。本综述全面讨论了 ZnT3 和中枢神经系统中囊泡锌的定位和功能。我们首先回顾锌稳态和运输的基本原理以及 ZnT3 的发现。然后,我们重点关注四个主要主题。I)锌能系统的解剖结构,包括其发育以及通过经验依赖性可塑性进行的调制。II)锌在细胞内信号转导中的作用,重点是锌如何影响神经递质受体和突触可塑性。III)缺乏 ZnT3 和因此缺乏囊泡锌的 ZnT3 KO 小鼠的行为特征。IV)ZnT3 和囊泡锌在健康和疾病中的作用。

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