Regulation and isoform function of the V-ATPases.
Regulation and isoform function of the V-ATPases.
复制标题
DOI：
10.1021/bi100397s
复制
发表时间：
2010-06-15
期刊：
影响因子：
2.9
通讯作者：
Forgac, Michael
中科院分区：
文献类型：
--
作者：
Toei, Masashi;Saum, Regina;Forgac, Michael
液泡(H+)-ATPase是依赖于ATP的质子泵，其功能是酸化细胞内的隔间，在某些情况下，通过真核细胞的质膜运输质子。细胞内V-ATPase在受体介导的内吞作用、细胞膜运输、激素原加工、蛋白质降解和小分子(如神经递质)的偶联摄取等正常生理过程中发挥重要作用。它们还在各种病原体的进入中发挥作用，包括许多包膜病毒，如流感病毒，以及毒素，如炭疽毒素。质膜V-ATPase在肾脏pH动态平衡、骨吸收、精子成熟以及肾小管性酸中毒、骨质疏松症和肿瘤转移等多种疾病过程中发挥作用。V-ATPase由一个外周的V1结构域和一个完整的V0结构域组成，V1结构域包含8个不同的亚基，负责ATP的水解，而V0结构域包含6个不同的亚基，负责转移质子。在哺乳动物细胞中，大多数V-ATPase亚基以多种异构体形式存在，这些亚基通常以组织特异性的方式表达。V0亚基之一(a亚基)的异构体已被证明具有针对不同细胞目的地的V-ATPase的信息。亚基a亚基异构体的突变导致人类疾病、骨质疏松症和肾小管性酸中毒。在体内调节V-ATPase活性的机制有很多，包括V1和V0结构域的可逆解离，控制质子转运和ATP水解的紧密耦合，以及选择性地将V-ATPase靶向不同的细胞膜。亚基a亚基的异构体通过偶联控制和选择性靶向参与调控。本文首先简要介绍了V-ATPase的功能、结构和机制，然后讨论了V-ATPase亚基异构体的作用和参与调节V-ATPase活性的机制。
The vacuolar (H+)-ATPases are ATP-dependent proton pumps that function to acidify intracellular compartments and, in some cases, transport protons across the plasma membrane of eukaryotic cells. Intracellular V-ATPases play an important role in such normal physiological processes as receptor-mediated endocytosis, intracellular membrane traffic, pro-hormone processing, protein degradation and the coupled uptake of small molecules, such as neurotransmitters. They also function in the entry of various pathogenic agents, including many envelope viruses, like influenza virus, and toxins, like anthrax toxin. Plasma membrane V-ATPases function in renal pH homeostasis, bone resorption and sperm maturation, as well as in various disease processes, including renal tubular acidosis, osteopetrosis and tumor metastasis. V-ATPases are composed of a peripheral V1 domain containing eight different subunits that is responsible for ATP hydrolysis and an integral V0 domain containing six different subunits that translocates protons. In mammalian cells most of the V-ATPase subunits exist in multiple isoforms which are often expressed in a tissue specific manner. Isoforms of one of the V0 subunits (subunit a) have been shown to possess information that targets the V-ATPase to distinct cellular destinations. Mutations in isoforms of subunit a lead to the human diseases osteopetrosis and renal tubular acidosis. A number of mechanisms are employed to regulate V-ATPase activity in vivo, including reversible dissociation of the V1 and V0 domains, control of the tightness of coupling of proton transport and ATP hydrolysis and selective targeting of V-ATPases to distinct cellular membranes. Isoforms of subunit a are involved in regulation both by control of coupling and by selective targeting. This review will begin with a brief introduction to the function, structure and mechanism of the V-ATPases followed by a discussion of the role of V-ATPase subunit isoforms and the mechanisms involved in regulation of V-ATPase activity.
登录
查看更多内容
影响因子：
30.8
作者：
Frattini, A;Orchard, PJ;Villa, A
通讯作者：
Villa, A
影响因子：
4.8
作者：
Bond, Sarah;Forgac, Michael
通讯作者：
Forgac, Michael
影响因子：
3.5
作者：
Cross, RL;Müller, V
通讯作者：
Müller, V
影响因子：
4.3
作者：
Gocheva, Vasilena;Joyce, Johanna A.
通讯作者：
Joyce, Johanna A.
影响因子：
4.8
作者：
Flannery, AR;Graham, LA;Stevens, TH
通讯作者：
Stevens, TH