ArticleProceedings of the National Academy of Sciences of the United States of America2016
Inositol pyrophosphates inhibit synaptotagmin-dependent exocytosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- The phosphate exporter XPR1 promotes gasdermin D-independent mature IL-1β secretion.The Journal of biological chemistry · 2026Article
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Isoliquiritigenin, a Bioactive Blood Component Derived from Licorice, Activates Nrf2 Enzymes to Confer Protection Against Radiation-Induced Nerve Injury.Antioxidants (Basel, Switzerland) · 2026Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders.Biomolecules · 2025Review
- The Use of Grating-Coupled Interferometry to Study Inositol Pyrophosphate-Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Absolute Configurations of Inositol Poly- and Pyrophosphates Assigned by Nuclear Magnetic Resonance Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Insights into the roles of inositol hexakisphosphate kinase 1 (IP6K1) in mammalian cellular processes.The Journal of biological chemistry · 2024Review
- Deleting IP6K1 stabilizes neuronal sodium-potassium pumps and suppresses excitability.Molecular brain · 2024Article
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Synthesis and biological evaluation of flavonoid-based IP6K2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System.Biomolecules · 2023Review
- Assigning the Absolute Configuration of Inositol Poly- and Pyrophosphates by NMR Using a Single Chiral Solvating Agent.Biomolecules · 2023Article
- Capillary electrophoresis mass spectrometry identifies new isomers of inositol pyrophosphates in mammalian tissues.Chemical science · 2023Article
- TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- One-pot chemical pyro- and tri-phosphorylation of peptides by using diamidophosphate in water.Chemical science · 2022Article
- Deletion of IP6K1 in mice accelerates tumor growth by dysregulating the tumor-immune microenvironment.Animal cells and systems · 2022Article
- Inositol hexakisphosphate kinases differentially regulate trafficking of vesicular glutamate transporters 1 and 2.Frontiers in cellular neuroscience · 2022Article
- 5-IPNature metabolism · 2021Article
- The Key Role of IPMolecules (Basel, Switzerland) · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 9 institutions in 4 countries.
Funding
Abstract
Inositol pyrophosphates such as 5-diphosphoinositol pentakisphosphate (5-IP7) are highly energetic inositol metabolites containing phosphoanhydride bonds. Although inositol pyrophosphates are known to regulate various biological events, including growth, survival, and metabolism, the molecular sites of 5-IP7 action in vesicle trafficking have remained largely elusive. We report here that elevated 5-IP7 levels, caused by overexpression of inositol hexakisphosphate (IP6) kinase 1 (IP6K1), suppressed depolarization-induced neurotransmitter release from PC12 cells. Conversely, IP6K1 depletion decreased intracellular 5-IP7 concentrations, leading to increased neurotransmitter release. Consistently, knockdown of IP6K1 in cultured hippocampal neurons augmented action potential-driven synaptic vesicle exocytosis at synapses. Using a FRET-based in vitro vesicle fusion assay, we found that 5-IP7, but not 1-IP7, exhibited significantly higher inhibitory activity toward synaptic vesicle exocytosis than IP6 Synaptotagmin 1 (Syt1), a Ca(2+) sensor essential for synaptic membrane fusion, was identified as a molecular target of 5-IP7 Notably, 5-IP7 showed a 45-fold higher binding affinity for Syt1 compared with IP6 In addition, 5-IP7-dependent inhibition of synaptic vesicle fusion was abolished by increasing Ca(2+) levels. Thus, 5-IP7 appears to act through Syt1 binding to interfere with the fusogenic activity of Ca(2+) These findings reveal a role of 5-IP7 as a potent inhibitor of Syt1 in controlling the synaptic exocytotic pathway and expand our understanding of the signaling mechanisms of inositol pyrophosphates.
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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.