ArticleThe Journal of biological chemistry2012
Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinity of synaptotagmin-1 by 40-fold.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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Who cites it
82 citing papers in PubMed.
- Electrostatics and Local Aromatic Residues Govern Lipid Binding and Membrane Penetration of Synaptotagmin C2 Domains.bioRxiv : the preprint server for biology · 2026Article
- Calcium-sensitive synaptotagmin 11-lipid interaction modulates exo-endocytosis.Nature communications · 2025Article
- Nanoengineered Calcium Receptors Coupled with Microscale Thermophoresis Enable Sensitive, Low-Volume Quantification of Calcium Ions in Complex Biological Fluids.ACS sensors · 2025Article
- MCOLN1/TRPML1-MCOLN3/TRPML3 heteromer and its coupling to CaAutophagy · 2025Article
- Independently engaging protein tethers of different length enhance synaptic vesicle trafficking to the plasma membrane.The Journal of physiology · 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
- The antimicrobial activity of ETD151 defensin is dictated by the presence of glycosphingolipids in the targeted organisms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dynamic formation of the protein-lipid prefusion complex.Biophysical journal · 2024Article
- The juxtamembrane linker of synaptotagmin 1 regulates CaNature communications · 2024Article
- Pancreatic β-cells package double C2-like domain beta protein into extracellular vesicles via tandem C2 domains.Frontiers in endocrinology · 2024Article
- Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm.Frontiers in cell and developmental biology · 2024Review
- The juxtamembrane linker of synaptotagmin 1 regulates CabioRxiv : the preprint server for biology · 2023Article
- Binding of perilipin 3 to membranes containing diacylglycerol is mediated by conserved residues within its PAT domain.The Journal of biological chemistry · 2023Article
- Protein-lipid interactions drive presynaptic assembly upstream of cell adhesion molecules.bioRxiv : the preprint server for biology · 2023Article
- Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.PLoS biology · 2023Article
- Simulations of active zone structure and function at mammalian NMJs predict that loss of calcium channels alone is not sufficient to replicate LEMS effects.Journal of neurophysiology · 2023Article
- Calcium Sensors of Neurotransmitter Release.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
- Synaptotagmin rings as high-sensitivity regulators of synaptic vesicle docking and fusion.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Synaptotagmin-1 is the main Ca(2+) sensor of neuronal exocytosis. It binds to both Ca(2+) and the anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)), but the precise cooperativity of this binding is still poorly understood. Here, we used microscale thermophoresis to quantify the cooperative binding of PIP(2) and Ca(2+) to synaptotagmin-1. We found that PIP(2) bound to the well conserved polybasic patch of the C2B domain with an apparent dissociation constant of ∼20 μM. PIP(2) binding reduced the apparent dissociation constant for Ca(2+) from ∼250 to <5 μM. Thus, our data show that PIP(2) makes synaptotagmin-1 >40-fold more sensitive to Ca(2+). This interplay between Ca(2+), synaptotagmin-1, and PIP(2) is crucial for neurotransmitter release.
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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.