The vacuolar (H+)-ATPases — nature's most versatile proton pumps

Nishi, Tsuyoshi; Forgac, Michael

doi:10.1038/nrm729

Cited by 1,103 publications

(1,138 citation statements)

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“…The former are electrochemically neutral because exchanges cations (NHEs) or anions (AEs), whilst the latter actively pumps H þ resulting in lumen or extracellular acidification. Ion exchangers and (V)H þ -ATPases can be both Golgi-resident and en route to the plasma membrane [Kellokumpu et al, 1988;Kopito, 1990;Moriyama and Nelson, 1998;Nishi and Forgac, 2002;Vitavska et al, 2003;Chen et al, 2004b]. By analogy to NHEs isoforms localized to the plasma membrane (NHE1) and endocytic compartments (NHE3 and NHE5) [Szaszi et al, 2000;Denker and Barber, 2002], Golgi-associated NHEs isoforms (NHE7 and NHE8) [Nakamura et al, 2005] might be regulated by the state of F-actin in the Golgi complex.…”

Section: Discussionmentioning

confidence: 99%

“…In the plasma membrane of red blood cells, an ankyrin/spectrin meshwork associates with anion exchanger 1 (AE1 or Band 3). This interaction is essential for the maintenance of the characteristic flattened shape of the cell and its mechanical stability [Marchesi, 1985;Nishi and Forgac, 2002]. Hence, in the Golgi complex, the potential ankyrin-interacting Golgi membrane protein anion exchanger 2 (AE2) [Holappa et al, 2001;Holappa and Kellokumpu, 2003] could provide a functional membrane anchorage site for the Golgi-associated spectrin/ ankyrin/actin cytoskeleton [De Matteis et al, 2000;Valderrama et al, 2000].…”

Section: Discussionmentioning

confidence: 99%

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Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

Lázaro‐Diéguez

Jiménez

Barth

et al. 2006

Cell Motil. Cytoskeleton

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Here we examine the contribution of actin dynamics to the architecture and pH of the Golgi complex. To this end, we have used toxins that depolymerize (cytochalasin D, latrunculin B, mycalolide B, and Clostridium botulinum C2 toxin) or stabilize (jasplakinolide) filamentous actin. When various clonal cell lines were examined by epifluorescence microscopy, all of these actin toxins induced compaction of the Golgi complex. However, ultrastructural analysis by transmission electron microscopy and electron tomography/three-dimensional modelling of the Golgi complex showed that F-actin depolymerization first induces perforation/fragmentation and severe swelling of Golgi cisternae, which leads to a completely disorganized structure. In contrast, F-actin stabilization results only in cisternae perforation/fragmentation. Concomitantly to actin depolymerization-induced cisternae swelling and disorganization, the intra-Golgi pH significantly increased. Similar ultrastructural and Golgi pH alkalinization were observed in cells treated with the vacuolar H þ -ATPases inhibitors bafilomycin A1 and concanamycin A. Overall, these results suggest that actin filaments are implicated in the preservation of the flattened shape of Golgi cisternae. This maintenance seems to be mediated by the regulation of the state of F-actin assembly on the Golgi pH homeostasis. Cell Motil. Cytoskeleton 63: 778-791, 2006. '

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

Lázaro‐Diéguez

Jiménez

Barth

et al. 2006

Cell Motil. Cytoskeleton

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“…The proton-translocating adenosine-triphosphatase (first observed in vacuolar membranes, hence called vacuolar proton-ATPase or V-ATPase) is nature's most universal proton pump found in all eukaryots (Finbow and Harrison 1997;Nishi and Forgac 2002;Cipriano et al 2008;Jefferies et al 2008). Similarly to the more familiar and related F-ATP synthase (FATPase) there are 3 catalytic sites, here for ATP hydrolysis, in the water soluble V 1 domain (F 1 domain in F-ATPase), and trans-membrane proton transport takes places in hydrophilic channels (or sacks) in the interface between the "c ring" and subunit a of the membrane bound V o (F o ) domain (Wilkens et al 1999;Grabe et al 2000;KawasakiNishi et al 2001;Wang et al 2004;Beyenbach and Wieczorek 2006) (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…In the case of V-ATPase rotation is driven by ATP binding and hydrolysis. One ATP molecule drives a 120 degrees rotation of the rotor and a transport of two protons from the cytoplasmic side to the "other" side, which can be the lumen of intracellular organs or the extracellular space, depending on the cellular location of V-ATPase (Finbow and Harrison 1997;Nishi and Forgac 2002;Beyenbach and Wieczorek 2006;Cipriano et al 2008;Jefferies et al 2008). This stoichiomerty is different form that of F-ATPase, in which there are ~12 c subunits, which have only 2 trans-membrane helices, each with a unique glutamic acid.…”

Section: Introductionmentioning

confidence: 99%

Estimating the rotation rate in the vacuolar proton-ATPase in native yeast vacuolar membranes

et al. 2012

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The rate of rotation of the rotor of the yeast vacuolar proton-ATPase (V-ATPase), relative to the stator or the steady parts of enzyme, is estimated in native vacuolar membrane vesicles of Saccharomyces cerevisiae under standardised conditions. Membrane vesicles are spontaneously formed after exposing purified yeast vacuoles to osmotic shock. The fraction of the total ATPase activity originating from V-ATPase is determined using the potent and specific inhibitor of the enzyme, concanamycin A. Inorganic phosphate liberated from ATP in the vacuolar membrane vesicle system, during 10 min of ATPase activity at 20 °C, is assayed spectrophotometrically for different concanamycin A concentrations. A fit to the quadratic binding equation, assuming a single concanamycin A binding site on a monomeric V-ATPase (our data is incompatible with models assuming more binding sites) to the inhibitor titration curve determines the concentration of the enzyme. Combining it with the known rotation:ATP stoichiometry of V-ATPase and the assayed concentration of inorganic phosphate liberated by V-ATPase leads to an average rate of ~9.53 Hz of the 360 degrees rotation, which, according to the time-dependence of the activity, extrapolates to ~14.14 Hz for the beginning of the reaction. These are low limit estimates. To our knowledge this is the first report of the rotation rate in a V-ATPase that is not subjected to genetic or chemical modification and it is not fixed on a solid support, instead it is functioning in its native membrane environment.Special Issue: Structure, function, folding and assembly of membrane proteins -Insight from Biophysics.

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“…The Vo component consists of a hydrogen channel, 17 kDa, and large, 116 kDa, protein with several transmembrane domains. This protein is crucial for membrane insertion, and four homologous genes encode variants of it [Nishi & Forgac, 2002]. The isoform TCIRG1 (ATP6i; A3) is amplified specifically in osteoclasts [Li et al, 1999;Mattsson et al, 2000].…”

Section: Bulk Calcium Transport By the Osteoclastmentioning

confidence: 99%

Calcium Signalling and Calcium Transport in Bone Disease

Blair

Schlesinger

Huang

et al.

Subcellular Biochemistry

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Calcium transport and calcium signalling mechanisms in bone cells have, in many cases, been discovered by study of diseases with disordered bone metabolism. Calcium matrix deposition is driven primarily by phosphate production, and disorders in bone deposition include abnormalities in membrane phosphate transport such as in chondrocalcinosis, and defects in phosphate-producing enzymes such as in hypophosphatasia. Matrix removal is driven by acidification, which dissolves the mineral. Disorders in calcium removal from bone matrix by osteoclasts cause osteopetrosis. On the other hand, although bone is central to management of extracellular calcium, bone is not a major calcium sensing organ, although calcium sensing proteins are expressed in both osteoblasts and osteoclasts. Intracellular calcium signals are involved in secondary control including cellular motility and survival, but the relationship of these findings to specific diseases is not clear. Intracellular calcium signals may regulate the balance of cell survival versus proliferation or anabolic functional response as part of signalling cascades that integrate the response to primary signals via cell stretch, estrogen, tyrosine kinase, and tumor necrosis factor receptors Keywords Hypophosphatasia; chondrocalcinosis; osteopetrosis; osteoporosis Although bone is not considered a major calcium sensing organ in humans, the cells of bone tissue control over 99% of the human body's calcium content. The principal calcium sensors that regulate bone calcium uptake and release are in the parathyroid glands. Bone function is also modified by vitamin D and by calcium transport in the kidney and intestine. These indirect mechanisms of controlling bone calcium metabolism are beyond the scope of our considerations here. In spite of processing such massive quantities of the Ca 2+ bone cells use calcium in their homeostatic control processes. The massive movement of calcium is carried out by specialized and regulated transporters. Defects in the transporters cause diseases with affect bone structure or function. Indeed, inborn errors have been very important in defining the calcium transport mechanisms in bone.Additionally, calcium is used by bone forming and bone degrading cells as a secondary mediator of hormone and cytokine action. These actions include roles in intercellular communication within groups of osteoblasts, which are connected by gap junctions [Henriksen et al., 2006]. These osteoblast groups function in a coordinated fashion in bone synthesis and maintenance, and are collectively known as the osteon. Osteoblasts in these groups are connected by gap junctions which are capable of propagating signals in the cell groups, including calcium waves [Xia and Ferrier, 1992]. Calcium is also an important regulator of

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The vacuolar (H+)-ATPases — nature's most versatile proton pumps

Cited by 1,103 publications

References 92 publications

Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

Estimating the rotation rate in the vacuolar proton-ATPase in native yeast vacuolar membranes

Calcium Signalling and Calcium Transport in Bone Disease

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