Rodman J, Feng Y, Myers M, Zhang J, Magner R, Forgac M
Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Ann N Y Acad Sci. 1994 Sep 15;733:203-11. doi: 10.1111/j.1749-6632.1994.tb17270.x.
The V-ATPases are a novel class of ATP-dependent proton pumps responsible for acidification of intracellular compartments in eukaryotic cells. They play an important role in receptor-mediated endocytosis, intracellular membrane traffic, macromolecular processing and degradation and coupled transport, as well as functioning in the plasma membrane of certain specialized cell types. The V-ATPases are multisubunit complexes that are organized into a peripheral V1 complex responsible for ATP hydrolysis and an integral V0 domain responsible for proton translocation. Regulation of vacuolar acidification is critical to its role in membrane traffic and other cellular processes. We are currently investigating several mechanisms of regulation of vacuolar acidification, including disulfide bond formation between cysteine residues located at the catalytic site, control of assembly of the peripheral and integral domains, and differential targeting of V-ATPases to different intracellular destinations using their interaction with organelle-specific adaptin complexes.
V-ATP酶是一类新型的ATP依赖性质子泵，负责真核细胞内细胞器的酸化。它们在受体介导的内吞作用、细胞内膜运输、大分子加工与降解以及偶联转运中发挥重要作用，并且在某些特殊细胞类型的质膜中也有功能。V-ATP酶是多亚基复合物，由负责ATP水解的外周V1复合物和负责质子转运的整合V0结构域组成。液泡酸化的调节对其在膜运输和其他细胞过程中的作用至关重要。我们目前正在研究液泡酸化调节的几种机制，包括位于催化位点的半胱氨酸残基之间形成二硫键、外周和整合结构域组装的控制，以及利用V-ATP酶与细胞器特异性衔接蛋白复合物的相互作用将其差异靶向到不同的细胞内目的地。
