ArticleMolecular biology of the cell2008
SNARE-catalyzed fusion events are regulated by Syntaxin1A-lipid interactions.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 157 citations in OpenAlex.
- Arachidonic Acid Structure and Synthesis.Reviews of physiology, biochemistry and pharmacology · 2027Review
- Computational design of membrane fusion proteins.bioRxiv : the preprint server for biology · 2026Article
- 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
- Designing New Natural-Mimetic Phosphatidic Acid: A Versatile and Innovative Synthetic Strategy for Glycerophospholipid Research.Angewandte Chemie (International ed. in English) · 2025Article
- PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- How SNARE proteins generate force to fuse membranes.Biophysical journal · 2025Article
- Cellular mechanisms of hormone secretion in neuroendocrine tumors: what goes wrong?Frontiers in cell and developmental biology · 2025Review
- Review
- Syntaxin 3B: A SNARE Protein Required for Vision.International journal of molecular sciences · 2024Review
- Phospholipase D1 produces phosphatidic acid at sites of secretory vesicle docking and fusion.Molecular biology of the cell · 2024Article
- Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm.Frontiers in cell and developmental biology · 2024Review
- SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023Article
- Functional regulation of syntaxin-1: An underlying mechanism mediating exocytosis in neuroendocrine cells.Frontiers in endocrinology · 2023Review
- Microautophagy Mediates Vacuolar Delivery of Storage Proteins in Maize Aleurone Cells.Frontiers in plant science · 2022Article
- CK2 Phosphorylation Is Required for Regulation of Syntaxin 1A Activity in CaInternational journal of molecular sciences · 2021Article
- Multifunctional Liposomes Modulate Purinergic Receptor-Induced Calcium Wave in Cerebral Microvascular Endothelial Cells and Astrocytes: New Insights for Alzheimer's disease.Molecular neurobiology · 2021Article
- Reduced Levels of miR-342-5p in Plasma Are Associated With Worse Cognitive Evolution in Patients With Mild Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
- Synaptic Function and Dysfunction in Lysosomal Storage Diseases.Frontiers in cellular neuroscience · 2021Article
- New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein.International journal of molecular sciences · 2020Review
- Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Membrane fusion is a process that intimately involves both proteins and lipids. Although the SNARE proteins, which ultimately overcome the energy barrier for fusion, have been extensively studied, regulation of the energy barrier itself, determined by specific membrane lipids, has been largely overlooked. Our findings reveal a novel function for SNARE proteins in reducing the energy barrier for fusion, by directly binding and sequestering fusogenic lipids to sites of fusion. We demonstrate a specific interaction between Syntaxin1A and the fusogenic lipid phosphatidic acid, in addition to multiple polyphosphoinositide lipids, and define a polybasic juxtamembrane region within Syntaxin1A as its lipid-binding domain. In PC-12 cells, Syntaxin1A mutations that progressively reduced lipid binding resulted in a progressive reduction in evoked secretion. Moreover, amperometric analysis of fusion events driven by a lipid-binding-deficient Syntaxin1A mutant (5RK/A) demonstrated alterations in fusion pore dynamics, suggestive of an energetic defect in secretion. Overexpression of the phosphatidic acid-generating enzyme, phospholipase D1, completely rescued the secretory defect seen with the 5RK/A mutant. Moreover, knockdown of phospholipase D1 activity drastically reduced control secretion, while leaving 5RK/A-mediated secretion relatively unaffected. Altogether, these data suggest that Syntaxin1A-lipid interactions are a critical determinant of the energetics of SNARE-catalyzed fusion events.
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