Synaptotagmin II Negatively Regulates Ca2+-triggered Exocytosis of Lysosomes in Mast Cells
Open accessAbstract
Synaptotagmins (Syts) I and II are believed to act as Ca2+ sensors in the control of neurotransmission. Here we demonstrate that mast cells express Syt II in their lysosomal fraction. We further show that activation of mast cells by either aggregation of FcεRI or by Ca2+ ionophores results in exocytosis of lysosomes, in addition to the well documented exocytosis of their secretory granules. Syt II directly regulates lysosomal exocytosis, whereby overexpression of Syt II inhibited Ca2+-triggered release of the lysosomal processed form of cathepsin D, whereas suppression of Syt II expression markedly potentiated this release. These findings provide evidence for a novel function of Syt II in negatively regulating Ca2+-triggered exocytosis of lysosomes, and suggest that Syt II–regulated secretion from lysosomes may play an important role in mast cell biology.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Syts constitute a group of membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis.
“Syts constitute a group of membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis (11, 23) and phagocytosis (11, 24, 25).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [23]
The Discussion (page not available) identifies Syt II as a regulator of lysosomal exocytosis in mast cells and proposes that it may control a granule-fusion event. Our copy does not establish a role for synaptotagmins in phagocytosis or specifically in vesicle docking. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse
Geppert, M., Goda, Y., Hammer, R. E., Li, C., Rosahl, T. W., Stevens, C. F., & Südhof, T. C. (1994) · Cell · doi:10.1016/0092-8674(94)90556-8 · Cited by 1,483 · see citing works
Mizuta, M., Kurose, T., Miki, T., Shoji-Kasai, Y., Takahashi, M., Seino, S., & Matsukura, S. (1997) · Diabetes · doi:10.2337/diab.46.12.2002 · Cited by 58 · see citing works
Flagged first, then by citations
Research works printed but not linked: 43
- [1]Stevens RL Austen KF Recent advance in the cellular and molecular biology of mast cells Immunol Today 1989 10 381 385 2692594
- [2]Galli SJ Gordon JR Wershil BK Cytokine production by mast cells and basophils Curr Opin Immunol 1991 3 865 872 1793528
- [3]Metcalfe DD Kaliner M Donlon MA The mast cell Crit Rev Immunol 1981 3 23 74 6178551
- [4]Malaviya R Ikeda T Ross E Abraham SN Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha Nature 1996 381 77 80 8609993
- [5]Prodeus AP Zhou X Maurer M Galli SJ Carroll MC Impaired mast cell-dependent natural immunity in complement C3-deficient mice Nature 1997 390 172 175 9367154
- [6]Echtenacher B Mannel DN Hultner L Critical protective role of mast cells in a model of acute septic peritonitis Nature 1996 381 75 77 8609992
- [7]Abraham SN Malaviya R Mast cells in infection and immunity Infect Immun 1997 65 3501 3508 9284112 PMC175499
- [8]Galli SJ The Paul Kallos memorial lecture. The mast cell: a versatile effector cell for a challenging world Int Arch Allergy Immunol 1997 113 14 22 9130474
- [9]Malaviya R Twesten NJ Ross EA Abraham SN Pfeifer JD Mast cells process bacterial Ags through a phagocytic route for class I MHC presentation to T cells J Immunol 1996 156 1490 1496 8568252
- [10]Frandji P Oskeritzian C Cacaraci F Lapeyre J Peronet R David B Guillet JG Mecheri S Antigen-dependent stimulation by bone marrow-derived mast cells of MHC class II-restricted T cell hybridoma J Immunol 1993 151 6318 6328 8245470
- [11]Gomperts BD Ge: a GTP-binding protein mediating exocytosis Annu Rev Physiol 1990 52 591 606 2109965
- [12]Aridor M Rajmilevich G Beaven MA Sagi-Eisenberg R Activation of exocytosis by the heterotrimeric G protein Gi3 Science 1993 262 1569 1572 7504324
- [13]Foreman JC Mongar JL Gomperts BD Calcium ionophores and movement of calcium ions following the physiological stimulus to a secretory process Nature 1973 245 249 251 4126372
- [14]Howell TW Cockcroft S Gomperts BD Essential synergy between calcium and guanine nucleotides in exocytotic secretion from permeabilized rat mast cells J Cell Biol 1987 105 191 198 2440894 PMC2114906
- [15]Bommert K Charlton MP DeBello WM Chin GJ Betz H Augustine GJ Inhibition of neurotransmitter release by C2-domain peptides implicates synaptotagmin in exocytosis Nature 1993 363 163 165 8097867
- [16]Brose N Petrenko AG Sudhof TC Jahn R Synaptotagmin: a calcium sensor on the synaptic vesicle surface Science 1992 256 1021 1025 1589771
- [17]DeBello WM Betz H Augustine GJ Synaptotagmin and neurotransmitter release Cell 1993 74 947 950 8104706
- [18]Elfernik LA Peterson MR Scheller RH A role for synaptotagmin (p65) in regulated exocytosis Cell 1993 72 153 159 8422678
- [20]Sudhof TC Rizo J Synaptotagmins: C2-domain proteins that regulate membrane traffic Neuron 1996 17 379 388 8816702
- [21]Chapman ER Hanson PI An S Jahn R Ca2+regulates the interaction between synaptotagmin and syntaxin 1 J Biol Chem 1995 270 23667 23671 7559535
- [22]Shao X Li C Fernandez I Zhang X Sudhof TC Rizo J Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch Neuron 1997 18 133 142 9010211
- [23]Li C Ullrich B Zhang JZ Anderson RG Brose N Sudhof TC Ca2+-dependent and -independent activities of neural and non-neural synaptotagmins Nature 1995 375 594 599 7791877
- [24]von Poser C Ichtchenko K Shao X Rizo J Sudhof TC The evolutionary pressure to inactivate. A subclass of synaptotagmins with an amino acid substitution that abolishes Ca2+binding J Biol Chem 1997 272 14314 14319 9162066
- [25]Lang J Fukuda M Zhang H Mikoshiba K Wollheim CB The first C2 domain of synaptotagmin is required for exocytosis of insulin from pancreatic beta-cells: action of synaptotagmin at low micromolar calcium EMBO (Eur Mol Biol Organ) J 1997 16 5837 5846 9312042 PMC1170215
- [27]Baram D Linial M Mekori YA Sagi-Eisenberg R Ca2+-dependent exocytosis in mast cells is stimulated by the Ca2+sensor, synaptotagmin I J Immunol 1998 161 5120 5123 9820478
- [28]Katz HR Dayton ET Levi SF Benson AC Austen KF Stevens RL Coculture of mouse IL-3-dependent mast cells with 3T3 fibroblasts stimulates synthesis of globopentaosylceramide (Forssman glycolipid) by fibroblasts and surface expression on both populations J Immunol 1988 140 3090 3097 2452198
- [29]Aridor M Traub LM Sagi-Eisenberg R Exocytosis in mast cells by basic secretagogues: evidence for direct activation of GTP-binding proteins J Cell Biol 1990 111 909 917 1697300 PMC2116270
- [30]Shore PA Burkhalter A Cohn VH A method for the fluorimetric assay of histamine in tissues J Pharmacol Exp Ther 1959 127 182 185 14446178
- [31]Geppert M Archer BT III Sudhof TC Synaptotagmin II. A novel differentially distributed form of synaptotagmin J Biol Chem 1991 266 13548 13552 1856191
- [32]Schwartz LB Austen KF Enzymes of the mast cell granule J Invest Dermatol 1980 74 349 353 6771334
- [33]Segal DM Taurog J Metzger H Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation Proc Natl Acad Sci USA 1977 74 2993 2997 70786 PMC431378
- [34]Rodriguez A Webster P Ortego J Andrews NW Lysosomes behave as Ca2+-regulated exocytic vesicles in fibroblasts and epithelial cells J Cell Biol 1997 137 93 104 9105039 PMC2139854
- [35]Nishimura Y Kato K Furuno K Himeno M Biosynthesis and processing of lysosomal cathepsin D in primary cultures of rat hepatocytes Biol Pharmacol Bull 1995 18 825 828 7550114
- [36]Mazingue C Dessaint JP Capron A [3H]serotonin release: an improved method to measure mast cell degranulation J Immunol Methods 1978 21 65 77 96185
- [37]Guo Z Turner C Castle D Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell surface projections regulates compound exocytosis in mast cells Cell 1998 94 537 548 9727496
- [38]Griffiths GM Secretory lysosomes-a special mechanism of regulated secretion in haemopoietic cells Trends Cell Biol 1996 6 329 332 15157429
- [39]Suarez QC The distribution of four lysosomal integral membrane proteins (LIMPs) in rat basophilic leukemia cells Tissue Cell 1987 19 495 504 3629578
- [40]Sannes PL Spicer SS The heterophagic granules of mast cells: dipeptidyl aminopeptidase II activity and resistance to exocytosis Am J Pathol 1979 94 447 457 426034 PMC2042257
- [41]Jamur MC Vugman I Hand AR Ultrastructural and cytochemical studies of acid phosphatase and trimetaphosphatase in rat peritoneal mast cells developing in vivo Cell Tissue Res 1986 244 557 563 3013411
- [42]Raposo G Tenza D Mecheri S Peronet R Bonnerot C Desaymard C Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation Mol Biol Cell 1997 8 2631 2645 9398681 PMC25733
- [43]Kim TD Eddlestone GT Mahmoud SF Kuchtey J Fewtrell C Correlating Ca2+responses and secretion in individual RBL-2H3 mucosal mast cells J Biol Chem 1997 272 31225 31229 9395446
- [44]Littleton JT Stern M Perin M Bellen HJ Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants Proc Natl Acad Sci USA 1994 91 10888 10892 7971978 PMC45131
- [45]Fox CC Jewell SD Whitacre CC Rat peritoneal mast cells present antigen to a PPD-specific T cell line Cell Immunol 1994 158 253 264 7916267
Cited by
Sorted by citations
Macrophage Cytokines: Involvement in Immunity and Infectious Diseases
Arango Duque, G., & Descoteaux, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00491 · Cited by 2,708 · see citing works
“Proc Natl Acad Sci U S A (2004) 101(23):8815–20.”
BackgroundBaram, D., Vaday, G. G., Salamon, P., Drucker, I., Hershkoviz, R., & Mekori, Y. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.7.4008 · Cited by 233 · see citing works
Self-citationSynaptotagmin XI regulates phagocytosis and cytokine secretion in macrophages
Arango Duque, G., Fukuda, M., & Descoteaux, A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202500 · Cited by 52 · see citing works
Synaptotagmin II could confer Ca2+ sensitivity to phagocytosis in human neutrophils
Lindmark, I. M., Karlsson, A., Serrander, L., Francois, P., Lew, D., Rasmusson, B., Stendahl, O., & Nüße, O. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(02)00209-4 · Cited by 28 · see citing works
- Authors
- Baram, D., Adachi, R., Medalia, O., Tuvim, M., Dickey, B. F., Mekori, Y. A., & Sagi-Eisenberg, R.
- Affiliations
- Tel Aviv University (IL)
- From the *Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel; the ‡Allergy and Clinical Immunology Unit, Sapir Medical Center, Kfar Saba, 44281, Israel; and the §Departments of Medicine and Cell Biology, Baylor College of Medicine, Houston, Texas 77030
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1999-05-17
- Volume
- 189
- Issue
- 10
- Pages
- 1649-1658
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2193646
- OpenAlex
- W2042316173
- Cited by
- 111
- References
- 2
- Citations by year
- 2025: 3 · 2024: 3 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 7 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 2 · 2012: 3
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation
- Tel Aviv University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- synaptotagmin II, mast cells, lysosomal exocytosis, calcium-triggered exocytosis, cathepsin D, calcium ionophore, lysosomes, secretory granules, calcium sensor
- MeSH terms
- Calcimycin, Animals, beta-N-Acetylhexosaminidases, Calcium, Cathepsin D, Cytoplasmic Granules, Exocytosis, Gene Expression Regulation, Lysosomes, Mast Cells, Mice, Inbred BALB C, Nerve Tissue Proteins, RNA, Messenger, Serotonin, Tetradecanoylphorbol Acetate, Transfection, Rats, Wistar, Receptors, IgE, Synaptotagmin II, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review