ArticleThe Journal of biological chemistry2016
Extracellular Polyphosphate Inhibits Proliferation in an Autocrine Negative Feedback Loop in Dictyostelium discoideum.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Phosphoproteomic Profiling Reveals Overlapping and Distinct Signaling Pathways inbioRxiv : the preprint server for biology · 2025Article
- Platelet Polyphosphate Signals Through NFκB to Induce Myofibroblast Differentiation.Biomolecules · 2025Article
- Two endogenousProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances in the cellular biology, biochemistry, and molecular biology of acidocalcisomes.Microbiology and molecular biology reviews : MMBR · 2024Review
- Proteomic Analysis of Dictyostelium discoideum by Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Evolutionary perspective on mammalian inorganic polyphosphate (polyP) biology.Biochemical Society transactions · 2023Review
- Starvation Induces Extracellular Accumulation of Polyphosphate inInternational journal of molecular sciences · 2023Article
- Dictyostelium discoideum cells retain nutrients when the cells are about to outgrow their food source.Journal of cell science · 2022Article
- Stabilization of Murine Norovirus by Bacteria.mSphere · 2022Article
- Effects of Polyphosphate on Leukocyte Function.Progress in molecular and subcellular biology · 2022Review
- The inositol pyrophosphate metabolism of Dictyostelium discoideum does not regulate inorganic polyphosphate (polyP) synthesis.Advances in biological regulation · 2022Article
- Article
- Review
- Model systems for studying polyphosphate biology: a focus on microorganisms.Current genetics · 2021Review
- Inorganic polyphosphates stimulates matrix production in human annulus fibrosus cells.JOR spine · 2021Article
- Polyphosphate is an extracellular signal that can facilitate bacterial survival in eukaryotic cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Platelet polyphosphate induces fibroblast chemotaxis and myofibroblast differentiation.Journal of thrombosis and haemostasis : JTH · 2020Article
- Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix.Chemical reviews · 2019Review
- Extracellular Polyphosphate Promotes Macrophage and Fibrocyte Differentiation, Inhibits Leukocyte Proliferation, and Acts as a Chemotactic Agent for Neutrophils.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Polyphosphate is a polymer of phosphate residues linked by high energy phosphoanhydride bonds. Despite being highly conserved throughout nature, its function is poorly understood. Here we show that Dictyostelium cells accumulate extracellular polyphosphate, and this acts to inhibit proliferation at high cell densities. In shaking culture, extracellular polyphosphate concentrations increase as cell density increases, and if the concentration of polyphosphate observed at the stationary phase is added to cells at mid-log, proliferation is halted. Adding an exopolyphosphatase to cell cultures or stationary phase conditioned medium decreases polyphosphate levels and abrogates the anti-proliferative effect. The cells show saturable binding of polyphosphate, suggesting the presence of a cell surface polyphosphate receptor. Extracellular polyphosphate accumulation is potentiated by decreased nutrient levels, potentially as a means to anticipate starvation. Loss of the Dictyostelium polyphosphate kinase DdPpk1 causes intracellular polyphosphate levels to become undetectable and negatively affects fitness, cytokinesis, and germination. However, cells lacking DdPpk1 accumulate ∼50% normal levels of extracellular polyphosphate, suggesting an additional means of synthesis. We found that cells lacking inositol hexakisphosphate kinase, which is responsible for the synthesis of the inositol pyrophosphates IP7 and IP8, reach abnormally high cell densities and show decreased extracellular polyphosphate levels. Two different enzymes thus appear to mediate the synthesis of Dictyostelium extracellular polyphosphate, which is used as a signal in an autocrine negative feedback loop to regulate cell proliferation.
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