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

      Current Opinion in Cell Biology
      Animals, Biological Transport, Cell Membrane, metabolism, Endosomes, Humans, Transport Vesicles, Vacuolar Proton-Translocating ATPases

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          Abstract

          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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          Most cited references76

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          The mechanisms of vesicle budding and fusion.

          Genetic and biochemical analyses of the secretory pathway have produced a detailed picture of the molecular mechanisms involved in selective cargo transport between organelles. This transport occurs by means of vesicular intermediates that bud from a donor compartment and fuse with an acceptor compartment. Vesicle budding and cargo selection are mediated by protein coats, while vesicle targeting and fusion depend on a machinery that includes the SNARE proteins. Precise regulation of these two aspects of vesicular transport ensures efficient cargo transfer while preserving organelle identity.
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            The vacuolar (H+)-ATPases--nature's most versatile proton pumps.

            The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including intracellular membrane transport, prohormone processing and transport of neurotransmitters, as well as the entry of many viruses into cells. The transporters responsible for controlling this crucial parameter in many intracellular compartments are the vacuolar (H+)-ATPases (V-ATPases). Recent advances in our understanding of the structure and regulation of the V-ATPases, together with the mapping of human genetic defects to genes that encode V-ATPase subunits, have led to tremendous excitement in this field.
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              The GTPase superfamily: a conserved switch for diverse cell functions.

              Proteins that bind and hydrolyse GTP are being discovered at a rapidly increasing rate. Each of these many GTPases acts as a molecular switch whose 'on' and 'off' states are triggered by binding and hydrolysis of GTP. Conserved structure and mechanism in myriad versions of the switch--in bacteria, yeast, flies and vertebrates--suggest that all derive from a single primordial protein, repeatedly modified in the course of evolution to perform a dazzling variety of functions.
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                Author and article information

                Journal
                18511251
                10.1016/j.ceb.2008.03.015

                Chemistry
                Animals,Biological Transport,Cell Membrane,metabolism,Endosomes,Humans,Transport Vesicles,Vacuolar Proton-Translocating ATPases

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