ArticleThe Journal of biological chemistry2014
The N- and C-terminal domains of tomosyn play distinct roles in soluble N-ethylmaleimide-sensitive factor attachment protein receptor binding and fusion regulation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed.
- Uncovering the Mechanisms of Intracellular Membrane Trafficking by Reconstituted Membrane Systems.Membranes · 2025Review
- Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes.Nature communications · 2024Article
- The Role of Tomosyn in the Regulation of Neurotransmitter Release.Advances in neurobiology · 2023Article
- Epigallocatechin gallate inhibits SNARE-dependent membrane fusion by blocking trans-SNARE assembly.FEBS open bio · 2022Article
- GLUT4 On the move.The Biochemical journal · 2022Article
- Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.Frontiers in endocrinology · 2022Review
- Genetic evidence for an inhibitory role of tomosyn in insulin-stimulated GLUT4 exocytosis.Traffic (Copenhagen, Denmark) · 2020Article
- GPCR regulation of secretion.Pharmacology & therapeutics · 2018Review
- BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction.Frontiers in molecular neuroscience · 2018Article
- Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Dynamic Partitioning of Synaptic Vesicle Pools by the SNARE-Binding Protein Tomosyn.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Tomosyn Negatively Regulates Arginine Vasopressin Secretion in Embryonic Stem Cell-Derived Neurons.PloS one · 2016Article
- Reconstituting Intracellular Vesicle Fusion Reactions: The Essential Role of Macromolecular Crowding.Journal of the American Chemical Society · 2015Article
- Molecular underpinnings of synaptic vesicle pool heterogeneity.Traffic (Copenhagen, Denmark) · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Tomosyn negatively regulates SNARE-dependent exocytic pathways including insulin secretion, GLUT4 exocytosis, and neurotransmitter release. The molecular mechanism of tomosyn, however, has not been fully elucidated. Here, we reconstituted SNARE-dependent fusion reactions in vitro to recapitulate the tomosyn-regulated exocytic pathways. We then expressed and purified active full-length tomosyn and examined how it regulates the reconstituted SNARE-dependent fusion reactions. Using these defined fusion assays, we demonstrated that tomosyn negatively regulates SNARE-mediated membrane fusion by inhibiting the assembly of the ternary SNARE complex. Tomosyn recognizes the t-SNARE complex and prevents its pairing with the v-SNARE, therefore arresting the fusion reaction at a pre-docking stage. The inhibitory function of tomosyn is mediated by its C-terminal domain (CTD) that contains an R-SNARE-like motif, confirming previous studies carried out using truncated tomosyn fragments. Interestingly, the N-terminal domain (NTD) of tomosyn is critical (but not sufficient) to the binding of tomosyn to the syntaxin monomer, indicating that full-length tomosyn possesses unique features not found in the widely studied CTD fragment. Finally, we showed that the inhibitory function of tomosyn is dominant over the stimulatory activity of the Sec1/Munc18 protein in fusion. We suggest that tomosyn uses its CTD to arrest SNARE-dependent fusion reactions, whereas its NTD is required for the recruitment of tomosyn to vesicle fusion sites through syntaxin interaction.
Indexed as
Identifiers
What OpenQuestion holds
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.