ArticleThe Journal of biological chemistry2008
The Ras/cAMP/protein kinase A pathway regulates glucose-dependent assembly of the vacuolar (H+)-ATPase in yeast.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.Aging cell · 2025Article
- The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease.Biomolecules · 2025Review
- Article
- V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.bioRxiv : the preprint server for biology · 2024Article
- An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.Molecular cancer research : MCR · 2024Article
- Yeast TLDc domain proteins regulate assembly state and subcellular localization of the V-ATPase.The EMBO journal · 2024Article
- Direct control of lysosomal catabolic activity by mTORC1 through regulation of V-ATPase assembly.Nature communications · 2022Article
- Review
- The Plant V-ATPase.Frontiers in plant science · 2022Review
- Genome-Wide Analysis of Nutrient Signaling Pathways Conserved in Arbuscular Mycorrhizal Fungi.Microorganisms · 2021Article
- Regulation and function of V-ATPases in physiology and disease.Biochimica et biophysica acta. Biomembranes · 2020Review
- Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer's Disease.International journal of molecular sciences · 2020Review
- The aging lysosome: An essential catalyst for late-onset neurodegenerative diseases.Biochimica et biophysica acta. Proteins and proteomics · 2020Review
- AKT Ser/Thr kinase increases V-ATPase-dependent lysosomal acidification in response to amino acid starvation in mammalian cells.The Journal of biological chemistry · 2020Article
- Interaction between the yeast RAVE complex and Vph1-containing VThe Journal of biological chemistry · 2020Article
- Cell organelles and yeast longevity: an intertwined regulation.Current genetics · 2020Review
- CD36 (SR-B2) as a Target to Treat Lipid Overload-Induced Cardiac Dysfunction.Journal of lipid and atherosclerosis · 2020Review
- Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK.Cell metabolism · 2019Article
- Caloric restriction controls stationary phase survival through Protein Kinase A (PKA) and cytosolic pH.Aging cell · 2019Article
- Reciprocal Regulation of V-ATPase and Glycolytic Pathway Elements in Health and Disease.Frontiers in physiology · 2019Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Vacuolar (H+)-ATPases (V-ATPases) are ubiquitous, ATP-driven proton pumps that acidify organelles or the extracellular space. A rapid and effective mechanism for regulating V-ATPase activity involves reversible dissociation of the two functional domains of the pump, V1 and V0. This process is best characterized in yeast, where V-ATPases are reversibly disassembled in response to glucose depletion. To identify regulators that control this process in vivo, a genetic screen was performed in yeast to search for mutants that cannot disassemble their V-ATPases when grown in the absence of glucose. This screen identified IRA1 (inhibitory regulator of the Ras/cAMP pathway 1) and IRA2 as essential genes for regulating V-ATPase dissociation in vivo. IRA1 and IRA2 encode GTPase-activating proteins that negatively regulate Ras in nutrient-poor conditions. Down-regulation of Ras lowers cAMP levels by reducing adenylate cyclase activity. Decreased cAMP levels in turn lead to reduced activity of protein kinase A (PKA). Our results show that targeted deletion of IRA2 results in defective disassembly of the V-ATPase in response to glucose depletion, and reexpression of the gene rescues this phenotype. Glucose-dependent dissociation is also blocked in strains expressing the dominant active RAS2val19 allele or in strains deficient for the regulatory subunit of PKA, both of which lead to constitutively active PKA. These results reveal a role for PKA in controlling glucose-dependent V-ATPase assembly in yeast.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.