ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Membrane penetration by synaptotagmin is required for coupling calcium binding to vesicle fusion in vivo.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 79 citations in OpenAlex.
- Disease-causing mutations in Synaptotagmin can act via dominant-negative, gain-of-function or haploinsufficient mechanisms.bioRxiv : the preprint server for biology · 2026Article
- The AD3 locus of synaptotagmin-1 C2 domains modulates domain stability.Biophysical journal · 2025Article
- Correlation between evoked neurotransmitter release and adaptive functions in SYT1-associated neurodevelopmental disorder.EBioMedicine · 2024Article
- c.1103T>C (p.Ile368Th) de novo Variant in Synaptotagmin 1 (International medical case reports journal · 2024Article
- Expanding the genetic and phenotypic spectrum of Baker-Gordon syndrome: a newJournal of genetics · 2024Article
- The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses.Communications biology · 2023Article
- The Dysferlin C2A Domain Binds PI(4,5)P2 and Penetrates Membranes.Journal of molecular biology · 2023Article
- Genetic disorders of neurotransmitter release machinery.Frontiers in synaptic neuroscience · 2023Review
- Calcium Sensors of Neurotransmitter Release.Advances in neurobiology · 2023Article
- 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
- Article
- Molecular Mechanisms Underlying Neurotransmitter Release.Annual review of biophysics · 2022Review
- Function of Drosophila Synaptotagmins in membrane trafficking at synapses.Cellular and molecular life sciences : CMLS · 2021Review
- SNARE Regulatory Proteins in Synaptic Vesicle Fusion and Recycling.Frontiers in molecular neuroscience · 2021Review
- Hypothesis Relating the Structure, Biochemistry and Function of Active Zone Material Macromolecules at a Neuromuscular Junction.Frontiers in synaptic neuroscience · 2021Article
- Synaptotagmin-1 membrane binding is driven by the C2B domain and assisted cooperatively by the C2A domain.Scientific reports · 2020Article
- Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The role of the C2A domain of synaptotagmin 1 in asynchronous neurotransmitter release.PloS one · 2020Article
- The C2A domain of synaptotagmin is an essential component of the calcium sensor for synaptic transmission.PloS one · 2020Article
- Structural basis for the clamping and CaNature communications · 2019Article
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10 authors at 3 institutions in 1 country.
Funding
Abstract
The vesicle protein synaptotagmin I is the Ca(2+) sensor that triggers fast, synchronous release of neurotransmitter. Specifically, Ca(2+) binding by the C(2)B domain of synaptotagmin is required at intact synapses, yet the mechanism whereby Ca(2+) binding results in vesicle fusion remains controversial. Ca(2+)-dependent interactions between synaptotagmin and SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment receptor) complexes and/or anionic membranes are possible effector interactions. However, no effector-interaction mutations to date impact synaptic transmission as severely as mutation of the C(2)B Ca(2+)-binding motif, suggesting that these interactions are facilitatory rather than essential. Here we use Drosophila to show the functional role of a highly conserved, hydrophobic residue located at the tip of each of the two Ca(2+)-binding pockets of synaptotagmin. Mutation of this residue in the C(2)A domain (F286) resulted in a ∼50% decrease in evoked transmitter release at an intact synapse, again indicative of a facilitatory role. Mutation of this hydrophobic residue in the C(2)B domain (I420), on the other hand, blocked all locomotion, was embryonic lethal even in syt I heterozygotes, and resulted in less evoked transmitter release than that in syt(null) mutants, which is more severe than the phenotype of C(2)B Ca(2+)-binding mutants. Thus, mutation of a single, C(2)B hydrophobic residue required for Ca(2+)-dependent penetration of anionic membranes results in the most severe disruption of synaptotagmin function in vivo to date. Our results provide direct support for the hypothesis that plasma membrane penetration, specifically by the C(2)B domain of synaptotagmin, is the critical effector interaction for coupling Ca(2+) binding with vesicle fusion.
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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.