The vacuolar (H+)-ATPase: subunit arrangement and in vivo regulation

  title={The vacuolar (H+)-ATPase: subunit arrangement and in vivo regulation},
  author={Jie Qi and Yanru Wang and Michael Forgac},
  journal={Journal of Bioenergetics and Biomembranes},
The V-ATPases are responsible for acidification of intracellular compartments and proton transport across the plasma membrane. They play an important role in both normal processes, such as membrane traffic, protein degradation, urinary acidification, and bone resorption, as well as various disease processes, such as viral infection, toxin killing, osteoporosis, and tumor metastasis. V-ATPases contain a peripheral domain (V1) that carries out ATP hydrolysis and an integral domain (V0… 
An update in the structure, function, and regulation of V-ATPases: the role of the C subunit
The C subunit has very important functions in terms of controlling the regulation of the reversible dissociation of V-ATPases.
An update in the structure, function, and regulation of V-ATPases: the role of the C subunit.
The C subunit has very important functions in terms of controlling the regulation of the reversible dissociation of V-ATPases.
The Synaptic Vesicle V-ATPase: A Regulatory Link Between Loading and Fusion?
This chapter outlines the molecular pharmacology of the V-ATPase and its role in the synaptic vesicle cycle, and focuses specifically on molecular interactions between V0 subunits and synaptic vESicle trafficking proteins and their relevance to late steps in neurotransmitter release.
Vacuolar acidification relies on the combined activity of endomembrane proton pumps
Insight is gained into the role of the V-PPase for vacuolar acidification and the increased biomass of the 35S:AVP1 line is not due to constitutive overexpression, since neither RNA nor protein level and enzyme activity were elevated.
Elucidating Vacuolar H+-ATPase Subunit Interactions: A Systematic Structural Analysis
It is proposed to narrow down the interaction regions to allow for future in silica drug discovery schemes to identify novel targets for development of anti-osteolytics.
V-ATPases: Rotary Engines for Transport and Traffic
This chapter pays particular attention to the dual function of the V-ATPase in transport and trafficking.
The Peripheral Stalk of Rotary ATPases
This review describes the information regarding the organization of the peripheral stalk components of F, A, and V-ATPases, highlighting the key differences between the studied enzymes, as well as the different processes in which the structure is involved.
The V-ATPase: small cargo, large effects.
RILP regulates vacuolar ATPase through interaction with the V1G1 subunit
The data demonstrate for the first time that RILP regulates the activity of the V-ATPase through its interaction with V1G1, a component of the peripheral stalk and is fundamental for correct V- ATPase assembly.
The V-ATPase a3 Subunit: Structure, Function and Therapeutic Potential of an Essential Biomolecule in Osteoclastic Bone Resorption
This review starts with an overview on bone, highlighting the role of V-ATPases in osteoclastic bone resorption, and goes in depth into the diverse role of the a subunit, not only in proton translocation but also in lipid binding, cell signaling and human diseases.


The V-type H+ ATPase: molecular structure and function, physiological roles and regulation
The V-type H+ ATPase is an ATP-driven enzyme that transforms the energy of ATP hydrolysis to electrochemical potential differences of protons across diverse biological membranes via the primary active transport of H+.
Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology
  • M. Forgac
  • Biology
    Nature Reviews Molecular Cell Biology
  • 2007
The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation, and the V-ATPases represent attractive and potentially highly specific drug targets.
Crystal structure of a central stalk subunit C and reversible association/dissociation of vacuole-type ATPase
  • M. Iwata, H. Imamura, S. Iwata
  • Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
The result shows that V-ATPase is substantially longer than the related F-type ATPase, due to the insertion of subunit C between the V1 (soluble) and the Vo (membrane bound) domains.
The RAVE Complex Is Essential for Stable Assembly of the Yeast V-ATPase*
Evidence supporting a role for RAVE in reassembly of the V-ATPase is provided but also an essential role in V- ATPase assembly under other conditions is demonstrated.
Arg-735 of the 100-kDa subunit a of the yeast V-ATPase is essential for proton translocation
It is suggested that Arg-735 is absolutely required for proton transport by the V-ATPases and is discussed in the context of a revised model of the topology of the 100-kDa subunit a.
Cysteine-mediated Cross-linking Indicates That Subunit C of the V-ATPase Is in Close Proximity to Subunits E and G of the V1 Domain and Subunit a of the V0 Domain*
Analysis of photocross-linked products by Western blot reveals that subunit E (part of V1) is in close proximity to both the head domain and foot domain of subunit C, consistent with a role for this subunit in controlling assembly of the V-ATPase complex.
The Where, When, and How of Organelle Acidification by the Yeast Vacuolar H+-ATPase
  • P. Kane
  • Biology
    Microbiology and Molecular Biology Reviews
  • 2006
Current knowledge of the structure, function, and regulation of the V- ATPase in S. cerevisiae is discussed and the relationship between biosynthesis and transport of V-ATPase and compartment-specific regulation of acidification is examined.
Microtubules Are Involved in Glucose-dependent Dissociation of the Yeast Vacuolar [H+]-ATPase in Vivo *
  • T. Xu, M. Forgac
  • Biology, Chemistry
    The Journal of Biological Chemistry
  • 2001
It is found that nocodazole, an agent that disrupts microtubules, partially blocked dissociation of the V-ATPase in response to glucose depletion in yeast, suggesting in vivo dissociation is not dependent upon cell cycle phase.
The Amino-terminal Domain of the Vacuolar Proton-translocating ATPase a Subunit Controls Targeting and in Vivo Dissociation, and the Carboxyl-terminal Domain Affects Coupling of Proton Transport and ATP Hydrolysis*
The results suggest that whereas targeting and in vivo dissociation are controlled by sequences located in the amino-terminal domains of the subunit a isoforms, coupling efficiency is controlled by the carboxyl-Terminal region.