ArticleThe Journal of cell biology2012
Munc13-4 reconstitutes calcium-dependent SNARE-mediated membrane fusion.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed.
- Munc13-4-STX7 inhibitors impair endosomal TLR activation and systemic inflammation.Nature chemical biology · 2026Article
- Lytic IFNγ is stored in cytotoxic granules and coreleased with granzyme B to mediate cytotoxic T lymphocyte killing.Cellular & molecular immunology · 2026Article
- Article
- Molecular requirements for mammalian crinophagy highlight a key role for CaResearch square · 2025Article
- Disruption of Retriever Function Impacts Retrograde Trafficking From Endosomes.Cell biology international · 2025Article
- Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells.Journal of translational medicine · 2024Article
- MADD regulates natural killer cell degranulation through Rab27a activation.Journal of cell science · 2024Article
- The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy.Genes & diseases · 2024Review
- Two roads diverged in a cell: insights from differential exosome regulation in polarized cells.Frontiers in cell and developmental biology · 2024Review
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
- Lytic granule exocytosis at immune synapses: lessons from neuronal synapses.Frontiers in immunology · 2023Review
- Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.Molecular cancer · 2022Review
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cytoskeletal Transport, Reorganization, and Fusion Regulation in Mast Cell-Stimulus Secretion Coupling.Frontiers in cell and developmental biology · 2021Review
- Unc-13 homolog D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a.Journal of cell science · 2020Article
- Molecular regulation of the plasma membrane-proximal cellular steps involved in NK cell cytolytic function.Journal of cell science · 2020Review
- Small GTPase ARF6 Is a Coincidence-Detection Code for RPH3A Polarization in Neutrophil Polarization.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host.International journal of molecular sciences · 2020Review
- Cross-regulation of defective endolysosome trafficking and enhanced autophagy through TFEB in UNC13D deficiency.Autophagy · 2019Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
Munc13-4 is a widely expressed member of the CAPS/Munc13 protein family proposed to function in priming secretory granules for exocytosis. Munc13-4 contains N- and C-terminal C2 domains (C2A and C2B) predicted to bind Ca(2+), but Ca(2+)-dependent regulation of Munc13-4 activity has not been described. The C2 domains bracket a predicted SNARE-binding domain, but whether Munc13-4 interacts with SNARE proteins is unknown. We report that Munc13-4 bound Ca(2+) and restored Ca(2+)-dependent granule exocytosis to permeable cells (platelets, mast, and neuroendocrine cells) dependent on putative Ca(2+)-binding residues in C2A and C2B. Munc13-4 exhibited Ca(2+)-stimulated SNARE interactions dependent on C2A and Ca(2+)-dependent membrane binding dependent on C2B. In an apparent coupling of membrane and SNARE binding, Munc13-4 stimulated SNARE-dependent liposome fusion dependent on putative Ca(2+)-binding residues in both C2A and C2B domains. Munc13-4 is the first priming factor shown to promote Ca(2+)-dependent SNARE complex formation and SNARE-mediated liposome fusion. These properties of Munc13-4 suggest its function as a Ca(2+) sensor at rate-limiting priming steps in granule exocytosis.
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