ArticleProceedings of the National Academy of Sciences of the United States of America2013
Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation.
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 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- TNFR1 links TNF exocytosis to TNF production in allergen-activated RBL-2H3 cells.Cellular signalling · 2023Article
- Exocytic machineries differentially control mediator release from allergen-triggered RBL-2H3 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Functional Roles of UNC-13/Munc13 and UNC-18/Munc18 in Neurotransmission.Advances in neurobiology · 2023Review
- Article
- Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells.Journal of molecular cell biology · 2021Article
- Cytoskeletal Transport, Reorganization, and Fusion Regulation in Mast Cell-Stimulus Secretion Coupling.Frontiers in cell and developmental biology · 2021Review
- ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization.Science advances · 2020Article
- Munc18-2, but not Munc18-1 or Munc18-3, regulates platelet exocytosis, hemostasis, and thrombosis.The Journal of biological chemistry · 2019Article
- Syntaxin 3, but not syntaxin 4, is required for mast cell-regulated exocytosis, where it plays a primary role mediating compound exocytosis.The Journal of biological chemistry · 2019Article
- Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis.Journal of immunology research · 2019Review
- Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells.The Journal of biological chemistry · 2018Article
- Diverse exocytic pathways for mast cell mediators.Biochemical Society transactions · 2018Review
- Bi-Allelic Mutations in STXBP2 Reveal a Complementary Role for STXBP1 in Cytotoxic Lymphocyte Killing.Frontiers in immunology · 2018Article
- PKC-dependent phosphorylation of Munc18a at Ser313 in activated RBL-2H3 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- Munc18a clusters SNARE-bearing liposomes prior toThe Biochemical journal · 2017Article
- SM protein Munc18-2 facilitates transition of Syntaxin 11-mediated lipid mixing to complete fusion for T-lymphocyte cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Conformational states of syntaxin-1 govern the necessity of N-peptide binding in exocytosis of PC12 cells and Caenorhabditis elegans.Molecular biology of the cell · 2016Article
- Article
- Differential Effects of Munc18s on Multiple Degranulation-Relevant Trans-SNARE Complexes.PloS one · 2015Article
- The biogenesis of lysosomes and lysosome-related organelles.Cold Spring Harbor perspectives in biology · 2014Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The function of the Munc18-1 protein hydrophobic pocket, which interacts with the syntaxin-1 N-terminal peptide, has been highly controversial in neurosecretion. Recent analysis of patients with familial hemophagocytic lymphohistiocytosis type 5 has identified the E132A mutation in the hydrophobic pocket of Munc18-2, prompting us to examine the role of this region in the context of immune cell secretion. Double knockdown of Munc18-1 and Munc18-2 in RBL-2H3 mast cells eliminates both IgE-dependent and ionomycin-induced degranulation and causes a significant reduction in syntaxin-11 without altering expressions of the other syntaxin isoforms examined. These phenotypes were effectively rescued on reexpression of wild-type Munc18-1 or Munc18-2 but not the mutants (F115E, E132A, and F115E/E132A) in the hydrophobic pocket of Munc18. In addition, these mutants show that they are unable to directly interact with syntaxin-11, as tested through protein interaction experiments. Our results demonstrate the crucial roles of the hydrophobic pocket of Munc18 in mast cell degranulation, which include the regulation of syntaxin-11. We also suggest that the functional importance of this region is significantly different between neuronal and immune cell exocytosis.
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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.