Zinc transport in the brain: Routes of zinc influx and efflux in neurons
Zinc transport in the brain: Routes of zinc influx and efflux in neurons
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DOI：
10.1093/jn/130.5.1484s
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发表时间：
2000-05-01
影响因子：
4.2
通讯作者：
Carter, PA
中科院分区：
文献类型：
--
作者：
Colvin, RA;Davis, N;Carter, PA
对锌在不同组织和细胞类型中的进入和退出途径的研究表明，锌可以使用几种退出或进入途径。在神经元中，已知的途径包括（1）当突触囊泡将其内容物排空到突触间隙中时，突触前释放沿着谷氨酸，（2）电压门控L型Ca 2+通道和谷氨酸门控通道，其在细胞去极化时提供进入途径并介导细胞外锌毒性，以及（3）质膜转运蛋白，其潜在地存在于对细胞锌稳态重要的所有神经元中，就机制而言，这些途径中了解最少的是转运蛋白途径。在静息状态下培养的神经元中锌摄取的动力学与质膜中存在的可饱和转运体一致，并表明其存在。负责质膜锌转运的蛋白质尚未明确确定。可能的候选者包括通过分子克隆鉴定的两种蛋白质，称为锌转运蛋白1和二价阳离子转运蛋白DCT 1，这两种蛋白质已被证明在脑中表达，但只有DCT 1被清楚地证明是转运蛋白，而锌转运蛋白1可能仅调节与尚未鉴定的蛋白质相关的锌转运。了解质膜锌转运的机制和神经调节将是全面了解神经元锌稳态的重要的第一步。
Studies of the routes of entry and exit for zinc in different tissues and cell types have shown that zinc can use several pathways of exit or entry. In neurons, known pathways include (1) presynaptic release along with glutamate when synaptic vesicles empty their contents into the synaptic cleft, (2) voltage-gated L-type Ca2+ channels and glutamate-gated channels that provide an entry route when cells are depolarized and that mediate extracellular zinc toxicity and (3) a plasma membrane transporter potentially present in all neurons important for cellular zinc homeostasis, The least understood of these pathways, in terms of mechanism, is the transporter pathway. The kinetics of zinc uptake in cultured neurons under resting conditions are consistent with and suggest the existence of a saturable transporter in the plasma membrane. The proteins responsible for plasma membrane zinc transport have not yet been definitely identified. Likely candidates include two proteins identified by molecular cloning termed zinc transporter 1 and divalent cation transporter DCT1, Both proteins have been shown to be expressed in the brain, but only DCT1 is clearly demonstrated to be a transport protein, whereas zinc transporter 1 may only modulate zinc transport in association with as-yet-unidentified proteins. Understanding the mechanism and neuromodulation of plasma membrane zinc transport will be an important first step toward a complete understanding of neuronal zinc homeostasis.