The signaling lipid PI(3,5)P2stabilizes V1–Vosector interactions and activates the V-ATPase

Li, Sheena; Diakov, Theodore T.; Xu, Tao; Tarsio, Maureen; Zhu, Wandi; Couoh‐Cardel, Sergio; Weisman, Lois S.; Kane, Patricia M.

doi:10.1091/mbc.e13-10-0563

Cited by 127 publications

(191 citation statements)

References 74 publications

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“…Moreover, lack of these sphingolipids is associated with instability of the V 1 -V 0 complex and impaired endocytic acidification. Recently, another membrane lipid species, phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P 2 ), has been identified to be important for V-ATPase activity (Li et al, 2014). Subunit a of the V 0 domain (Vph1p in yeast) interacts with PtdIns(3,5)P 2 and is recruited from the cytosol to the membrane when PtdIns(3,5)P 2 levels peak in endocytic compartments.…”

Section: Regulation Of V-atpase Functionmentioning

confidence: 99%

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

Maxson

Grinstein

2014

Journal of Cell Science

204

196

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The vacuolar H + -ATPase (V-ATPase) has long been appreciated to function as an electrogenic H + pump. By altering the pH of intracellular compartments, the V-ATPase dictates enzyme activity, governs the dissociation of ligands from receptors and promotes the coupled transport of substrates across membranes, a role often aided by the generation of a transmembrane electrical potential. In tissues where the V-ATPase is expressed at the plasma membrane, it can serve to acidify the extracellular microenvironment. More recently, however, the V-ATPase has been implicated in a bewildering variety of additional roles that seem independent of its ability to translocate H + . These non-canonical functions, which include fusogenicity, cytoskeletal tethering and metabolic sensing, are described in this Cell Science at a Glance article and accompanying poster, together with a brief overview of the conventional functions of the V-ATPase.

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Section: Regulation Of V-atpase Functionmentioning

confidence: 99%

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

Maxson

Grinstein

2014

Journal of Cell Science

204

196

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“…Recent studies have begun to elucidate the mechanisms that allow cells to communicate extracellular signals to intracellular V-ATPases located at the vacuolar membrane. In yeast, V-ATPase assembly is regulated by glucose, pH, and osmotic stress, and it is intertwined with glycolysis, RAS/cyclic AMP (cAMP)/protein kinase A (PKA), and phosphatidylinositol-(3,5)-bisphosphate [PI(3,5) P 2 ] (16,(18)(19)(20)(21). In insects, starvation and hormone stimulation influence V 1 V o assembly by mechanisms involving cAMP/ PKA signaling (9,22,23).…”

Section: Acuolar Hmentioning

confidence: 99%

“…At pH 7.0, V-ATPase disassembly is significantly suppressed compared to disassembly at pH 5.0, the optimal pH for yeast growth. Although the mechanisms involved in the prevention of disassembly by pH remain elusive, adaptation to high pH appears to have both PI(3,5)P 2 -dependent and -independent components (16). Knowing whether glucose and pH use common mechanisms to regulate V 1 V o disassembly requires additional studies.…”

Section: Yeast V-atpase: At the Crossroads Of Multiple Intracellular mentioning

confidence: 99%

“…Exposure of yeast to osmotic shock increases the total pool of vacuolar V 1 V o assembled (89). This involves a mechanism that requires the signaling lipid PI(3,5)P 2 interacting with the V o subunit a isoform Vph1p (16). Interestingly, PI(3,5)P 2 has little or no effect on glucose-dependent reversible disassembly of the VATPase, indicating that the cellular signals behind hyperosmotic stress-and glucose-induced V-ATPase reassembly are independent.…”

Section: Yeast V-atpase: At the Crossroads Of Multiple Intracellular mentioning

confidence: 99%

“…However, not all V-ATPases appear to disassemble and reassemble. V-ATPase subunit isoforms and V-ATPase interactions with an assembly factor (RAVE; discussed below) in the cytosol and phosphoinositides at the membrane can dictate which pumps reversibly disassemble in response to environmental cues (16,17). Recent studies have begun to elucidate the mechanisms that allow cells to communicate extracellular signals to intracellular V-ATPases located at the vacuolar membrane.…”

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confidence: 99%

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Saccharomyces cerevisiae Vacuolar H ⁺ -ATPase Regulation by Disassembly and Reassembly: One Structure and Multiple Signals

Parra

Chan

2014

Eukaryot Cell

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Vacuolar H؉ -ATPases (V-ATPases) are highly conserved ATP-driven proton pumps responsible for acidification of intracellular compartments. V-ATPase proton transport energizes secondary transport systems and is essential for lysosomal/vacuolar and endosomal functions. These dynamic molecular motors are composed of multiple subunits regulated in part by reversible disassembly, which reversibly inactivates them. Reversible disassembly is intertwined with glycolysis, the RAS/cyclic AMP (cAMP)/ protein kinase A (PKA) pathway, and phosphoinositides, but the mechanisms involved are elusive. The atomic-and pseudoatomic-resolution structures of the V-ATPases are shedding light on the molecular dynamics that regulate V-ATPase assembly. Although all eukaryotic V-ATPases may be built with an inherent capacity to reversibly disassemble, not all do so. V-ATPase subunit isoforms and their interactions with membrane lipids and a V-ATPase-exclusive chaperone influence V-ATPase assembly. This minireview reports on the mechanisms governing reversible disassembly in the yeast Saccharomyces cerevisiae, keeping in perspective our present understanding of the V-ATPase architecture and its alignment with the cellular processes and signals involved. V acuolar Hϩ -ATPases (V-ATPases) are ATP-driven proton pumps distributed throughout the endomembrane system of all eukaryotic cells (1, 2). V-ATPase proton transport acidifies organelles and energizes secondary transport systems. Zymogen activation, protein processing and trafficking, and receptor-mediated endocytosis are fundamental cellular processes that require V-ATPase activity. Cells specialized for active proton secretion express also V-ATPases at the plasma membrane. Proton transport by plasma membrane V-ATPases in osteoclasts, epididymal clear cells, and renal intercalated cells is necessary for bone resorption, sperm maturation, and maintenance of the systemic acidbase balance, respectively (3, 4). V-ATPase has been implicated in several pathological states, including osteopetrosis, distal renal tubular acidosis, male infertility, and cancers (2). Not surprisingly, studies of V-ATPase function and regulation are increasing, as is our knowledge of these dynamic proteins.V-ATPase structure and function are highly conserved and well characterized in Saccharomyces cerevisiae (referred to here as yeast). Lack of V-ATPase function leads to a conditionally lethal phenotype that is characterized by pH sensitivity in yeast; complete lack of V-ATPase function is lethal in higher eukaryotes (5). Recent atomic-and pseudo-atomic-resolution structures of VATPase and its subunits have helped shed light on the molecular dynamics that regulate V-ATPase function (6, 7). V-ATPases are large multisubunit complexes structurally organized into two major domains, V 1 and V o (Fig. 1). Eight peripheral subunits (A to H) form the V 1 domain, where ATP hydrolysis takes place. Six subunits (a, c, c=, cЉ, d, and e) comprise V o , the membrane intrinsic domain that forms the path for proton transport. An impo...

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Novel defect in phosphatidylinositol 4‐kinase type 2‐alpha (PI4K2A) at the membrane‐enzyme interface is associated with metabolic cutis laxa

Mohamed

Gardeitchik

Balasubramaniam

et al. 2020

J of Inher Metab Disea

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The signaling lipid PI(3,5)P₂stabilizes V₁–V_osector interactions and activates the V-ATPase

Cited by 127 publications

References 74 publications

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

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

Saccharomyces cerevisiae Vacuolar H ⁺ -ATPase Regulation by Disassembly and Reassembly: One Structure and Multiple Signals

Novel defect in phosphatidylinositol 4‐kinase type 2‐alpha (PI4K2A) at the membrane‐enzyme interface is associated with metabolic cutis laxa

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The signaling lipid PI(3,5)P2stabilizes V1–Vosector interactions and activates the V-ATPase

Cited by 127 publications

References 74 publications

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

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

Saccharomyces cerevisiae Vacuolar H + -ATPase Regulation by Disassembly and Reassembly: One Structure and Multiple Signals

Novel defect in phosphatidylinositol 4‐kinase type 2‐alpha (PI4K2A) at the membrane‐enzyme interface is associated with metabolic cutis laxa

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Product

Resources

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The signaling lipid PI(3,5)P₂stabilizes V₁–V_osector interactions and activates the V-ATPase

Saccharomyces cerevisiae Vacuolar H ⁺ -ATPase Regulation by Disassembly and Reassembly: One Structure and Multiple Signals