ArticleProceedings of the National Academy of Sciences of the United States of America2013
Prevalent mechanism of membrane bridging by synaptotagmin-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Independently engaging protein tethers of different length enhance synaptic vesicle trafficking to the plasma membrane.The Journal of physiology · 2025Article
- Structural insights into lipid membrane binding by human ferlins.The EMBO journal · 2025Article
- Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1.Biophysical journal · 2025Article
- Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1.bioRxiv : the preprint server for biology · 2024Article
- On the difficulties of characterizing weak protein interactions that are critical for neurotransmitter release.FEBS open bio · 2022Review
- Article
- Polybasic Patches in Both C2 Domains of Synaptotagmin-1 Are Required for Evoked Neurotransmitter Release.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- The neuronal calcium sensor Synaptotagmin-1 and SNARE proteins cooperate to dilate fusion pores.eLife · 2021Article
- Membrane Association and Functional Mechanism of Synaptotagmin-1 in Triggering Vesicle Fusion.Biophysical journal · 2020Article
- CaeLife · 2020Article
- Synaptotagmin-1 and Doc2b Exhibit Distinct Membrane-Remodeling Mechanisms.Biophysical journal · 2020Article
- Interference of pH buffer with PbMetallomics : integrated biometal science · 2020Article
- Phosphatidylinositol 4,5 Bisphosphate Controls the cis and trans Interactions of Synaptotagmin 1.Biophysical journal · 2019Article
- Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Membrane-Binding Cooperativity and Coinsertion by C2AB Tandem Domains of Synaptotagmins 1 and 7.Biophysical journal · 2019Article
- Mechanism of neurotransmitter release coming into focus.Protein science : a publication of the Protein Society · 2018Review
- The high-affinity calcium sensor synaptotagmin-7 serves multiple roles in regulated exocytosis.The Journal of general physiology · 2018Review
- Synaptotagmin-1 drives synchronous CaNature neuroscience · 2018Article
- Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 CProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Non-Native Metal Ion Reveals the Role of Electrostatics in Synaptotagmin 1-Membrane Interactions.Biochemistry · 2017Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Synaptotagmin-1 functions as a Ca(2+) sensor in neurotransmitter release through its two C2 domains (the C2A and C2B domain). The ability of synaptotagmin-1 to bridge two membranes is likely crucial for its function, enabling cooperation with the soluble N-ethylmaleimide sensitive factor adaptor protein receptors (SNAREs) in membrane fusion, but two bridging mechanisms have been proposed. A highly soluble synaptotagmin-1 fragment containing both domains (C2AB) was shown to bind simultaneously to two membranes via the Ca(2+)-binding loops at the top of both domains and basic residues at the bottom of the C2B domain (direct bridging mechanism). In contrast, a longer fragment including a linker sequence (lnC2AB) was found to aggregate in solution and was proposed to bridge membranes through trans interactions between lnC2AB oligomers bound to each membrane via the Ca(2+)-binding loops, with no contact of the bottom of the C2B domain with the membranes. We now show that lnC2AB containing impurities indeed aggregates in solution, but properly purified lnC2AB is highly soluble. Moreover, cryo-EM images reveal that a majority of lnC2AB molecules bridge membranes directly. Fluorescence spectroscopy indicates that the bottom of the C2B domain contacts the membrane in a sizeable population of molecules of both membrane-bound C2AB and membrane-bound lnC2AB. NMR data on nanodiscs show that a fraction of C2AB molecules bind to membranes with antiparallel orientations of the C2 domains. Together with previous studies, these results show that direct bridging constitutes the prevalent mechanism of membrane bridging by both C2AB and lnC2AB, suggesting that this mechanism underlies the function of synaptotagmin-1 in neurotransmitter release.
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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.