Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University.
Program in Cell and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University.
Front Biosci (Landmark Ed). 2017 Jan 1;22(4):609-622. doi: 10.2741/4506.
V-ATPases are ATP-driven proton pumps present in both intracellular and cell surface membranes of eukaryotes that function in many normal and disease processes. V-ATPases are large, multi-subunit complexes composed of a peripheral domain (V) that hydrolyzes ATP and a membrane integral domain (V) that translocates protons. Because of the diversity of their functions, V-ATPase activity is controlled by a number of mechanisms. Regulated assembly of the V and V domains rapidly modulates V-ATPase activity in response to a variety of cues, including nutrient availability, growth factor stimulation and cellular differentiation. Considerable information has recently emerged concerning the cellular signaling pathways controlling regulated assembly. Acid secretion by epithelial cells in the kidney and epididymus is controlled by regulated trafficking of V-ATPases to the cell surface. Isoforms of subunit a of the V domain both control trafficking of V-ATPases to distinct cellular membranes and confer properties to the resultant complexes that help account for differences in pH between cellular compartments. Finally, differential expression of genes encoding V-ATPases subunits occurs in a number of contexts, including cancer.
V-ATPases 是一种存在于真核细胞的细胞内和细胞膜表面的 ATP 驱动质子泵，在许多正常和疾病过程中发挥作用。V-ATPases 是一种由外周结构域 (V) 和膜整合结构域 (V) 组成的大型多亚基复合物，其中 V 结构域水解 ATP，而 V 结构域则转运质子。由于其功能的多样性，V-ATPase 的活性受到多种机制的调节。V 和 V 结构域的调节组装可快速响应多种信号，包括营养物质的可用性、生长因子的刺激和细胞分化，从而调节 V-ATPase 的活性。最近，有关控制调节组装的细胞信号通路的信息大量涌现。肾脏和附睾上皮细胞的酸分泌受 V-ATPase 向细胞表面的调节性转运控制。V 结构域亚基 a 的同工型既控制 V-ATPase 向不同细胞膜的转运，又赋予产生的复合物特性，有助于解释细胞区室之间 pH 值的差异。最后，编码 V-ATPase 亚基的基因在包括癌症在内的许多情况下的表达存在差异。
