The vacuolar-type H+-ATPase at a glance – more than a proton pump

Maxson, Michelle E.; Grinstein, Sergio

doi:10.1242/jcs.158550

Cited by 200 publications

(199 citation statements)

References 93 publications

(103 reference statements)

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“…Carnell and colleagues described the first mechanistic model of how WASH-dependent actin polymerization directly controls protein sorting in Dictyostelium lysosomes . In Dictyostelium, WASH physically associates with the V-ATPase, a key H + pump that is crucial for the establishment and maintenance of the acidic pH in endosomes and lysosomes (Maxson and Grinstein, 2014). WASH directly drives the removal of V-ATPase from lysosomes and its recycling to small vesicles.…”

Section: Research Articlementioning

confidence: 99%

“…Normally, endosomes and, in particular, lysosomes get acidified by the activity of the vacuolar (V)-ATPase, a large multimeric ATP-dependent H + pump (Maxson and Grinstein, 2014). An acidic environment provides not only an optimal pH for a wide range of acidic hydrolases but also ensures that internalized receptors release their ligands so that they can recycle back to the plasma membrane (Luzio et al, 2007;Pryor and Luzio, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Nagel

Bechtold

Rodríguez

et al. 2017

Journal of Cell Science

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The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH; also known as Washout in flies) is a conserved actin-nucleationpromoting factor controlling Arp2/3 complex activity in endosomal sorting and recycling. Previous studies have identified WASH as an essential regulator in Drosophila development. Here, we show that homozygous wash mutant flies are viable and fertile. We demonstrate that Drosophila WASH has conserved functions in integrin receptor recycling and lysosome neutralization. WASH generates actin patches on endosomes and lysosomes, thereby mediating both aforementioned functions. Consistently, loss of WASH function results in cell spreading and cell migration defects of macrophages, and an increased lysosomal acidification that affects efficient phagocytic and autophagic clearance. WASH physically interacts with the vacuolar (V)-ATPase subunit Vha55 that is crucial to establish and maintain lysosome acidification. As a consequence, starved flies that lack WASH function show a dramatic increase in acidic autolysosomes, causing a reduced lifespan. Thus, our data highlight a conserved role for WASH in the endocytic sorting and recycling of membrane proteins, such as integrins and the V-ATPase, that increase the likelihood of survival under nutrient deprivation.

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Section: Research Articlementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Nagel

Bechtold

Rodríguez

et al. 2017

Journal of Cell Science

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“…V-ATPase is a highly conserved multi-subunit enzyme that uses energy from ATP hydrolysis to transport protons across membranes [2][3][4]. It consists of two major functional domains, V 1 and V 0 (Fig.…”

Section: Structure Of V-atpasementioning

confidence: 99%

“…V-ATPase is also involved in a variety of acidification-independent processes [3,4]. The best example is vacuolar assembly, in which membrane-encircled lysosome-associated organelles fuse to form larger compartments.…”

Section: V-atpase In Signaling and Endocytosismentioning

confidence: 99%

Role of vacuolar-type proton ATPase in signal transduction

Sun‐Wada

Wada

2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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The vacuolar H(+)-ATPase (V-ATPase) was first identified as an electrogenic proton pump that acidifies the lumen of intra- and extracellular compartments. The acidic pH generated by V-ATPase is important for a wide range of cellular processes as well as acidification-independent processes such as secretion and membrane fusion. In addition to these housekeeping functions, recent studies implicate V-ATPase in the direct regulation and function of signaling pathways. In this review, we describe recent findings on the functions of V-ATPase in growth regulation and tissue physiology.

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“…⌬pH and ⌬⌿ will also affect proteins and nucleic acids in the nucleus. In addition, it is likely that the V-type ATPase will be found to be involved in numerous other processes (6). This is the first study to demonstrate that the V-type ATPase subunits are in the NE, an important finding on its own.…”

mentioning

confidence: 71%

Nuclear V-type ATPase. Focus on “Vacuolar H⁺-ATPase in the nuclear membranes regulates nucleo-cytosolic proton gradients”

Cuppoletti

2016

American Journal of Physiology-Cell Physiology

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THE NUCLEAR ENVELOPE (NE) consists of two continuous membranes, with pores where the inner nuclear membrane (INM) meets the outer nuclear membrane (ONM) (7). V-type ATPases in the plasma membrane and intracellular membranes alter pH (⌬pH) and generate a transmembrane electrical potential (⌬⌿) across plasma membranes and intracellular compartments (6).In the accompanying article by Santos et al. (8) published in this issue of the American Journal of Physiology-Cell Physiology, the authors tested the hypothesis that the V-type ATPase was present and functional in the NE. The authors established that the nuclear pH is acidic, pH gradients across the nuclear membrane were bafilomycin and concanamycin sensitive and that the V-type ATPase was present in the NE by immunolocalization, and in both the ONM and INM by Western blots and ATPase assays.The flow of ions across the nuclear membranes is restricted (3). Prior studies to determine whether there was an electrochemical gradient of protons across the nuclear membrane were contradictory and no previous studies examined whether V-type ATPases might be involved. The authors used the ratiometric dye SNARF-1 to determine nuclear-cytoplasmic pH gradients. They examined RWPE-1 cells, a prostate epithelial cell line, LNCaP cells, a prostate cancer cell line, and highly tumorigenic and invasive CL-2 cells derived from LNCaP cells. They found that the steady-state pH of the nucleus was more acidic than the cytosol in RWPE-1 cells and LNCaP cells, but there was no difference in the steady-state pH between the nucleus and cytosol in CL-2 cells. The authors attribute the differences in their findings from those of others who also used ratiometric approaches to the failure of others to carry out in situ calibration for each cell type and each cell. In the present study, the authors used individual in situ calibration procedures for nucleus and cytosol, respectively, in contrast to other studies, which used either a single calibration curve obtained in vitro or in situ or the average of in situ calibration curves for nucleus and cytosol. The authors could have made a stronger case for their attribution of their differences from the studies of others by documenting how the different approach would change the measurements and by documenting that an average calibration could recapitulate the contradictory finding of others using SNARF-1.They found that absolute pH values varied in the various compartments among cells, so all values were also reported as ⌬pH. No differences were seen in the outward gradients between RWPE-1, LNCaP, and CL-2 cells in aggregate. However, there were larger inward H ϩ gradients in CL-2 cells than RWPE-1 or LNCaP cells, in aggregate. When ⌬pH was given as a percentage for each cell type, the majority of each cell type showed no ⌬pH, but a larger percentage of CL-2 cells than RWPE-1 cells had inward H ϩ gradients. The differences in ⌬pH among the cell types and between individual cells suggest that there are unknown mechanisms for regulation of the pH of the...

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The vacuolar-type H+-ATPase at a glance – more than a proton pump

Cited by 200 publications

References 93 publications

Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Role of vacuolar-type proton ATPase in signal transduction

Nuclear V-type ATPase. Focus on “Vacuolar H⁺-ATPase in the nuclear membranes regulates nucleo-cytosolic proton gradients”

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The vacuolar-type H+-ATPase at a glance – more than a proton pump

Cited by 200 publications

References 93 publications

Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization

Role of vacuolar-type proton ATPase in signal transduction

Nuclear V-type ATPase. Focus on “Vacuolar H+-ATPase in the nuclear membranes regulates nucleo-cytosolic proton gradients”

Contact Info

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Nuclear V-type ATPase. Focus on “Vacuolar H⁺-ATPase in the nuclear membranes regulates nucleo-cytosolic proton gradients”