The V-type H+-ATPase in vesicular trafficking: targeting, regulation and function. Curr Opin Cell Biol

Program in Membrane Biology, Center for Systems Biology, Simches Research Center, CPZN No. 8212, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
Current Opinion in Cell Biology (Impact Factor: 8.47). 09/2008; 20(4):415-26. DOI: 10.1016/
Source: PubMed


Vacuolar-type H+-ATPase (V-ATPase)-driven proton pumping and organellar acidification is essential for vesicular trafficking along both the exocytotic and endocytotic pathways of eukaryotic cells. Deficient function of V-ATPase and defects of vesicular acidification have been recently recognized as important mechanisms in a variety of human diseases and are emerging as potential therapeutic targets. In the past few years, significant progress has been made in our understanding of function, regulation, and the cell biological role of V-ATPase. Here, we will review these studies with emphasis on novel direct roles of V-ATPase in the regulation of vesicular trafficking events.

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Available from: Masamitsu Futai, Jan 26, 2014
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    • "Involved in cellular trafficking, exocytosis and endocytosis, and interaction with the cytoskeleton (Marshansky and Futai 2008) "
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    • "V-ATPase is indispensable to an organism's growth under normal conditions because of its role in secondary transport and maintenance of solute homeostasis and its proposed role in facilitating vesicle fusion. Studies have shown a large spectrum of subunit V-ATPase isoforms in mammals (Marshansky and Futai, 2008). In insects, this protein has been reported to be highly expressed in the Malpighian tubules of Aedes aegypti (Weng et al., 2003), and after exposure to thermal stress condition, their energy metabolism and water balance change immediately to protect them from death. "
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    • "Comparisons of ATP free energy with electrochemical membrane potential or directly measured work output indicate thermodynamic efficiency close to 100% (Junge et al., 2009). V-ATPases are found in all eukaryotic cells (Forgac, 2007) driving acidification essential to the function of endosomes, lysosomes, and the Golgi apparatus (Marshansky and Futai, 2008). Inhibition blocks endosomal transit and arrests recycling of receptor-ligand complexes. "
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    ABSTRACT: Vacuolar H(+)-ATPases are multisubunit complexes that operate with rotary mechanics and are essential for membrane proton transport throughout eukaryotes. Here we report a ∼1 nm resolution reconstruction of a V-ATPase in a different conformational state from that previously reported for a lower-resolution yeast model. The stator network of the V-ATPase (and by implication that of other rotary ATPases) does not change conformation in different catalytic states, and hence must be relatively rigid. We also demonstrate that a conserved bearing in the catalytic domain is electrostatic, contributing to the extraordinarily high efficiency of rotary ATPases. Analysis of the rotor axle/membrane pump interface suggests how rotary ATPases accommodate different c ring stoichiometries while maintaining high efficiency. The model provides evidence for a half channel in the proton pump, supporting theoretical models of ion translocation. Our refined model therefore provides new insights into the structure and mechanics of the V-ATPases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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