Mechanism and regulation of cellular zinc transport
Mechanism and regulation of cellular zinc transport
复制标题
DOI：
10.2119/2007-00037.sekler
复制
发表时间：
2007-07-01
影响因子：
5.7
通讯作者：
Silverman, William F.
中科院分区：
文献类型：
--
作者：
Sekler, Israel;Sensi, Stefano L.;Silverman, William F.
锌是高达10%的哺乳动物蛋白质的活性和折叠的必需辅因子，并且可以调节许多其他蛋白质的功能。由于锌对细胞生理学的各个方面的多效性作用，由锌缺乏或其细胞浓度过度升高引起的细胞锌含量的不足可以具有灾难性的后果，并且与包括糖尿病和中风在内的主要病理生理学有关。因此，细胞锌的浓度需要建立离散的、活跃的细胞梯度。锌在细胞器中的细胞分布被精确地管理，以提供每个细胞隔室所需的锌浓度。锌稳态的复杂性反映在几乎每个细胞室中发现的锌稳态蛋白的种类和数量惊人。鉴于它们的普遍性和重要性，令人惊讶的是，锌转运蛋白的功能，调节和串扰的许多方面都知之甚少。在这篇简短的综述中，我们将重点介绍在质膜和囊泡隔室中产生生理上适当的锌梯度所需的机制和参与者。我们还将强调一些未解决的问题，关于他们在细胞锌稳态的作用。
Zinc is an essential cofactor for the activity and folding of up to ten percent of mammalian proteins and can modulate the function of many others, Because of the pleiotropic effects of zinc on every aspect of cell physiology, deficits of cellular zinc content, resulting from zinc deficiency or excessive rise in its cellular concentration, can have catastrophic consequences and are linked to major patho-physiologies including diabetes and stroke. Thus, the concentration of cellular zinc requires establishment of discrete, active cellular gradients. The cellular distribution of zinc into organelles is precisely managed to provide the zinc concentration required by each cell compartment. The complexity of zinc homeostasis is reflected by the surprisingly large variety and number of zinc homeostatic proteins found in virtually every cell compartment. Given their ubiquity and importance, it is surprising that many aspects of the function, regulation, and crosstalk by which zinc transporters operate are poorly understood. In this mini-review, we will focus on the mechanisms and players required for generating physiologically appropriate zinc gradients across the plasma membrane and vesicular compartments. We will also highlight some of the unsolved issues regarding their role in cellular zinc homeostasis.