ArticleThe Journal of cell biology2008
Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion.
Article in The Journal of cell biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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Who cites it
132 citing papers in PubMed, 223 citations in OpenAlex.
- Spatial organization of phosphoinositide signaling.FEBS letters · 2026Review
- A PIP2-stabilized syntaxin-1a structure mapped with transition metal ion FRET and unnatural fluorescent amino acids at the plasma membrane.Structure (London, England : 1993) · 2026Article
- Calcium-sensitive synaptotagmin 11-lipid interaction modulates exo-endocytosis.Nature communications · 2025Article
- Nanoscale clustering and dynamics of phosphatidylinositol 4,5-bisphosphate in an immune cell model.Biophysical journal · 2025Article
- PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Intracellular protein-lipid interactions drive presynaptic assembly prior to neurexin recruitment.Neuron · 2025Article
- MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Beyond the MUN domain, Munc13 controls priming and depriming of synaptic vesicles.Cell reports · 2024Article
- Membrane Proteins and Membrane Curvature: Mutual Interactions and a Perspective on Disease Treatments.Biomolecules · 2023Review
- Molecular basis of PIP2-dependent conformational switching of phosphorylated CD44 in binding FERM.Biophysical journal · 2023Article
- SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023Article
- PI(4,5)P2-dependent and -independent roles of PI4P in the control of hormone secretion by pituitary cells.Frontiers in endocrinology · 2023Review
- SARS-CoV-2 Envelope Protein Forms Clustered Pentamers in Lipid Bilayers.Biochemistry · 2022Article
- Phorbolester-activated Munc13-1 and ubMunc13-2 exert opposing effects on dense-core vesicle secretion.eLife · 2022Article
- Complexin-1 and synaptotagmin-1 compete for binding sites on membranes containing PtdInsPBiophysical journal · 2022Article
- Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalkChemical science · 2022Article
- Localization of the Priming Factors CAPS1 and CAPS2 in Mouse Sensory Neurons Is Determined by Their N-Termini.Frontiers in molecular neuroscience · 2022Article
- Acyl-chain saturation regulates the order of phosphatidylinositol 4,5-bisphosphate nanodomains.Communications chemistry · 2021Article
- Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021Review
- α-Synuclein plasma membrane localization correlates with cellular phosphatidylinositol polyphosphate levels.eLife · 2021Article
72 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Phosphatidylinositol 4,5-bisphosphate (PI 4,5-P(2)) on the plasma membrane is essential for vesicle exocytosis but its role in membrane fusion has not been determined. Here, we quantify the concentration of PI 4,5-P(2) as approximately 6 mol% in the cytoplasmic leaflet of plasma membrane microdomains at sites of docked vesicles. At this concentration of PI 4,5-P(2) soluble NSF attachment protein receptor (SNARE)-dependent liposome fusion is inhibited. Inhibition by PI 4,5-P(2) likely results from its intrinsic positive curvature-promoting properties that inhibit formation of high negative curvature membrane fusion intermediates. Mutation of juxtamembrane basic residues in the plasma membrane SNARE syntaxin-1 increase inhibition by PI 4,5-P(2), suggesting that syntaxin sequesters PI 4,5-P(2) to alleviate inhibition. To define an essential rather than inhibitory role for PI 4,5-P(2), we test a PI 4,5-P(2)-binding priming factor required for vesicle exocytosis. Ca(2+)-dependent activator protein for secretion promotes increased rates of SNARE-dependent fusion that are PI 4,5-P(2) dependent. These results indicate that PI 4,5-P(2) regulates fusion both as a fusion restraint that syntaxin-1 alleviates and as an essential cofactor that recruits protein priming factors to facilitate SNARE-dependent fusion.
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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.