The vacuolar H+-ATPase: a universal proton pump of eukaryotes

Finbow, Malcolm E.; Harrison, Michael A.

doi:10.1042/bj3240697

Cited by 237 publications

(188 citation statements)

References 230 publications

(253 reference statements)

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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%

“…Indeed, these and other highly homologous proteins belong to the same class, that we termed ductins (Finbow et al 1994;Dunlop et al 1995;Finbow et al 1995;Saito et al 1998;Bohrmann and Bonafede 2001). In a number studies on a 16kDa gap junctional protein isolated from lobster, which is not only a ductin protein but it can substitute subunit c of the yeast V-ATPase functionally in a hybrid construct (Finbow et al 1993;Finbow and Harrison 1997), we have shown that the c ring is a hexameric assembly of 4-helix trans-membrane bundles (Holzenburg et al 1993;Pali et al 1995), determined the vertical membrane location of the unique glutamic acid and shown it to contact lipids (Pali et al 1997;Pali et al 1999), and discovered a metal binding site (Pali et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…The ATP6V1G2 gene encodes one of two characterized isoforms of the 13 kDa G-subunit of the multicomponent vacuolar ATPase (V-ATPase), a membrane-associated proton pump with critical roles in the regulation of the cytosolic pH and acidification of intracellular organelles. 21 This acidification is central to a number of fundamental cell functions such as protein sorting and degradation, generation of secretory granules and endocytosis, and is known to be important for inflammatory and immune cell differentiation and function. Salt stress causes an increase in the expression of V-ATPase subunit-encoding transcripts in higher plants.…”

Section: Discussionmentioning

confidence: 99%

Haplotype-specific gene expression profiles in a telomeric major histocompatibility complex gene cluster and susceptibility to autoimmune diseases

et al. 2006

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The telomeric class III region of the major histocompatibility complex is gene dense, but apart from the three tumour necrosis factor (TNF) superfamily members (TNF, lymphotoxin alpha and lymphotoxin beta) little is known of the expression and function of the majority of the genes. Recent genetic studies in autoimmune diseases, particularly rheumatoid arthritis (RA), have suggested a human leukocyte antigen (HLA)-DR-independent disease effect in this region. To gain further insights into these associations, we used lipopolysaccharide-stimulated human macrophages to examine inducible mRNA expression and genotype-phenotype relationships for genes in this region. Following stimulation in addition to the expected induction of TNF mRNA, a 14-fold increase of ATP6V1G2 at 18 h (Po0.001) was seen, whereas B-associated transcript (BAT)2 (Po0.001) and leucocyte-specific transcript (LST)1 (Po0.001) were both downregulated. By genotyping single-nucleotide polymorphisms spanning a 70 kb interval centred on the TNF locus, we constructed haplotypes and determined associated expression profiles for 10 genes in the cluster using quantitative real-time polymerase chain reaction. Overexpression of BAT1 mRNA was associated with carriers of a haplotype containing the LST1 marker transmitted to RA cases in a family study and also DRB1*15 associated with susceptibility to nephritis in systemic lupus erythematosus. The implications of our findings for the understanding of genetic associations with disease susceptibility in this region are discussed.

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“…It was described in detail in the 1980s and 90s [Boyer, 1997]. The F1 or V1 assemblies are nano-motors that couple ATP hydrolysis to electrogenic H+ translocation [Finbow and Harrison, 1997]. The F and V-ATPases are electrogenic and transport H + without counter-ions.…”

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+-ATPase: a universal proton pump of eukaryotes

Cited by 237 publications

References 230 publications

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

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

Haplotype-specific gene expression profiles in a telomeric major histocompatibility complex gene cluster and susceptibility to autoimmune diseases

Calcium Signalling and Calcium Transport in Bone Disease

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