Department of Biological Sciences, Ohio University, Athens, OH 45701, USA.
Metallomics. 2010 May;2(5):306-17. doi: 10.1039/b926662c. Epub 2010 Apr 16.
Our knowledge of the molecular mechanisms of intracellular homeostatic control of zinc ions is now firmly grounded on experimental findings gleaned from the study of zinc proteomes and metallomes, zinc transporters, and insights from the use of computational approaches. A cell's repertoire of zinc homeostatic molecules includes cytosolic zinc-binding proteins, transporters localized to cytoplasmic and organellar membranes, and sensors of cytoplasmic free zinc ions. Under steady state conditions, a primary function of cytosolic zinc-binding proteins is to buffer the relatively large zinc content found in most cells to a cytosolic zinc(ii) ion concentration in the picomolar range. Under non-steady state conditions, zinc-binding proteins and transporters act in concert to modulate transient changes in cytosolic zinc ion concentration in a process that is called zinc muffling. For example, if a cell is challenged by an influx of zinc ions, muffling reactions will dampen the resulting rise in cytosolic zinc ion concentration and eventually restore the cytosolic zinc ion concentration to its original value by shuttling zinc ions into subcellular stores or by removing zinc ions from the cell. In addition, muffling reactions provide a potential means to control changes in cytosolic zinc ion concentrations for purposes of cell signalling in what would otherwise be considered a buffered environment not conducive for signalling. Such intracellular zinc ion signals are known to derive from redox modifications of zinc-thiolate coordination environments, release from subcellular zinc stores, and zinc ion influx via channels. Recently, it has been discovered that metallothionein binds its seven zinc ions with different affinities. This property makes metallothionein particularly well positioned to participate in zinc buffering and muffling reactions. In addition, it is well established that metallothionein is a source of zinc ions under conditions of redox signalling. We suggest that the biological functions of transient changes in cytosolic zinc ion concentrations (presumptive zinc signals) complement those of calcium ions in both spatial and temporal dimensions.
我们对细胞内锌离子稳态控制的分子机制的了解，现在已经牢固地建立在从锌蛋白质组和金属组学、锌转运体的研究中获得的实验发现，以及从计算方法的应用中获得的见解的基础上。细胞的锌稳态分子组成包括细胞质锌结合蛋白、定位于细胞质和细胞器膜的转运体，以及细胞质游离锌离子的传感器。在稳态条件下，细胞质锌结合蛋白的主要功能是将大多数细胞中相对较大的锌含量缓冲到细胞内锌(ii)离子浓度的皮摩尔范围内。在非稳态条件下，锌结合蛋白和转运体协同作用，调节细胞质锌离子浓度的瞬时变化，这一过程称为锌掩蔽。例如，如果细胞受到锌离子流入的挑战，掩蔽反应将减弱细胞质锌离子浓度升高的幅度，并最终通过将锌离子转运到细胞内储存库或从细胞中去除锌离子，将细胞质锌离子浓度恢复到原始值。此外，掩蔽反应为控制细胞内锌离子浓度的变化提供了一种潜在的方法，以实现细胞信号传递，否则在缓冲环境中不利于信号传递。这种细胞内锌离子信号被认为来源于锌-硫醇配位环境的氧化还原修饰、亚细胞锌库的释放以及通过通道的锌离子内流。最近，人们发现金属硫蛋白以不同的亲和力结合其七个锌离子。这种特性使金属硫蛋白特别适合参与锌缓冲和掩蔽反应。此外，已经证实金属硫蛋白是氧化还原信号条件下锌离子的来源。我们认为细胞质锌离子浓度（假定的锌信号）的瞬态变化的生物学功能在空间和时间维度上与钙离子的功能互补。
