Synaptotagmin II could confer Ca2+ sensitivity to phagocytosis in human neutrophils
Open accessAbstract
Phagolysosome fusion and granule exocytosis in neutrophils are calcium-dependent processes. The calcium requirements vary between granule types, suggesting the presence of different calcium sensors. The synaptotagmins, a family of calcium-binding proteins, previously shown to participate in vesicle fusion and vesicle recycling in excitable cells, are putative calcium-sensors of exocytosis in excitable cells. In this study, we show that synaptotagmin II is present in human neutrophils and may participate in phagocytic and in exocytotic processes. In protein extracts from human neutrophils, we identified synaptotagmin II by Western blot as an 80 kDa protein. Subcellular fractionation revealed that synaptotagmin II was associated with the specific granules. In fMLP-stimulated cells, synaptotagmin II translocated to the plasma membrane. This correlated with the upregulation of complement receptor 3 (CR 3), reflecting the translocation of specific granules to the cell surface. Synaptotagmin II also translocated to the phagosome after complement-mediated phagocytosis in the presence of calcium. LAMP-1 translocated in parallel but probably was located to another subcellular compartment than synaptotagmin II. Under calcium-reduced conditions, neither synaptotagmin II nor LAMP-1 translocated to the phagosome. We therefore suggest a role for synaptotagmin II as calcium-sensor during phagocytosis and secretion in neutrophils.
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?
Ca2+-binding synaptotagmin VII, as well as synaptotagmins II and XI, are associated with phagosome formation and biogenesis including the link between phagosomes and lysosomes.
“In this context, the Ca2+-binding synaptotagmin VII, which is linked to VAMP7 function in exocytosis, as well as the synaptotagmins II and XI have also been associated with phagosome formation and biogenesis including the link between phagosomes and lysosomes (17–19).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [18]
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
SNAP receptors implicated in vesicle targeting and fusion
Söllner, T. H., Whiteheart, S. W., Brunner, M., Erdjument‐Bromage, H., Geromanos, S. J., Tempst, P., & Rothman, J. E. (1993) · Nature · doi:10.1038/362318a0 · Cited by 3,239 · see citing works
Mechanisms of intracellular protein transport
Rothman, J. E. (1994) · Nature · doi:10.1038/372055a0 · Cited by 2,283 · see citing works
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
Ca2+-dependent and -independent activities of neural and non-neural synaptotagmins
Li, C., Ullrich, B., Zhang, J. Z., Anderson, R. G. W., Brose, N., & Südhof, T. C. (1995) · Nature · doi:10.1038/375594a0 · Cited by 599 · see citing works
Creutz, C. E. (1992) · Science · doi:10.1126/science.1439804 · Cited by 559 · see citing works
Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin
Nonet, M. L., Grundahl, K. M., Meyer, B. J., & Rand, J. B. (1993) · Cell · doi:10.1016/0092-8674(93)90357-v · Cited by 537 · see citing works
Littleton, J., Stern, M., Schulze, K., Perin, M., & Bellen, H. J. (1993) · Cell · doi:10.1016/0092-8674(93)90733-7 · Cited by 463 · see citing works
Focal Exocytosis of Vamp3-Containing Vesicles at Sites of Phagosome Formation
Bajno, L., Peng, X., Schreiber, A. D., Moore, H.-P. H., Trimble, W. S., & Grinstein, S. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.3.697 · Cited by 319 · see citing works
Human neutrophil granules and secretory vesicles
Borregaard, N., Lollike, K., Kjeldsen, L., Sengeløv, H., Bastholm, L., Nielsen, M. H., & Bainton, D. F. (1993) · European Journal Of Haematology · doi:10.1111/j.1600-0609.1993.tb00629.x · Cited by 295 · see citing works
Subcellular localization and dynamics of Mac-1 (alpha m beta 2) in human neutrophils.
Sengeløv, H., Kjeldsen, L., Diamond, M., Springer, T. A., & Borregaard, N. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116724 · Cited by 286 · see citing works
Lew, P. D., Monod, A., Waldvogel, F. A., Dewald, B., Baggiolini, M., & Pozzan, T. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.102.6.2197 · Cited by 242 · see citing works
Borregaard, N., Kieldsen, L., Sengeloev, H., Diamond, M., Springer, T. A., Anderson, H. C., Kishimoto, T., & Bainton, D. F. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.56.1.80 · Cited by 231 · see citing works
Jaconi, M. E., Lew, D. P., Carpentier, J. L., Magnusson, K., Sjögren, M., & Stendahl, O. I. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.110.5.1555 · Cited by 225 · see citing works
Self-citationIntracellular Free Calcium Localization in Neutrophils During Phagocytosis
Sawyer, D. W., Sullivan, J. A., & Mandell, G. L. (1985) · Science · doi:10.1126/science.4048951 · Cited by 213 · see citing works
Characterization of SNARE protein expression in beta cell lines and pancreatic islets
Wheeler, M. B., Sheu, L., Ghai, M., Bouquillon, A., Grondin, G., Weller, U., Beaudoin, A. R., Bennett, M. K., Trimble, W. S., & Gaisano, H. Y. (1996) · Endocrinology · doi:10.1210/endo.137.4.8625909 · Cited by 210 · see citing works
Ca2+-dependent and Ca2+-independent phagocytosis in human neutrophils
Lew, D. P., Andersson, T., HED, J., Virgilio, F. D., Pozzan, T., & Stendahl, O. I. (1985) · Nature · doi:10.1038/315509a0 · Cited by 207 · see citing works
Self-citationSynaptic Core Complex of Synaptobrevin, Syntaxin, and SNAP25 Forms High Affinity -SNAP Binding Site
McMahon, H. T., & Südhof, T. C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.2213 · Cited by 174 · see citing works
A modified procedure for the determination of loukocyte alkaline phosphatase
DeChatelet, L. R., & Cooper, M. R. (1970) · Biochemical Medicine · doi:10.1016/0006-2944(70)90103-1 · Cited by 161 · see citing works
Nielsen, S., Marples, D. D. R., Birn, H., Mohtashami, M., Dalby, N. O., Trimble, M. E., & Knepper, M. A. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118229 · Cited by 155 · see citing works
Involvement of SNAP-23 and syntaxin 6 in human neutrophil exocytosis
Martı́n-Martı́n, B., Nabokina, S. M., Blasi, J., Lazo, P. A., & Mollinedo, F. (2000) · Blood · doi:10.1182/blood.v96.7.2574 · Cited by 141 · see citing works
Brumell, J. H., Volchuk, A., Sengeløv, H., Borregaard, N., Cieutat, A.-M., Bainton, D. F., Grinstein, S., & Klip, A. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.12.5750 · Cited by 140 · see citing works
Distinct Ca2+ and Sr2+ Binding Properties of Synaptotagmins
Li, C., Davletov, B., & Südhof, T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.24898 · Cited by 129 · see citing works
Subcellular fractionation of human neutrophils on Percoll density gradients
Kjeldsen, L., Sengeløv, H., & Borregaard, N. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(99)00171-4 · Cited by 124 · see citing works
SNAP‐25 is present in a SNARE complex in adrenal chromaffin cells
Roth, D., & Burgoyne, R. D. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00833-7 · Cited by 113 · see citing works
Synaptotagmin II Negatively Regulates Ca2+-triggered Exocytosis of Lysosomes in Mast Cells
Baram, D., Adachi, R., Medalia, O., Tuvim, M., Dickey, B. F., Mekori, Y. A., & Sagi-Eisenberg, R. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.10.1649 · Cited by 111 · see citing works
Cieutat, A.-M., Lobel, P., August, J. T., Kjeldsen, L., Sengeløv, H., Borregaard, N., & Bainton, D. F. (1998) · Blood · doi:10.1182/blood.v91.3.1044.1044_1044_1058 · Cited by 108 · see citing works
Synaptotagmins: more isoforms than functions?
Schiavo, G., Osborne, S. L., & Sgouros, J. (1998) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.1998.8527 · Cited by 108 · see citing works
Cytosolic Free Calcium and the Cytoskeleton in the Control of Leukocyte Chemotaxis
Pettit, E. J., & Fay, F. S. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.4.949 · Cited by 104 · see citing works
Synaptotagmins in membrane traffic: which vesicles do the tagmins tag?
Marquèze, B., Berton, F., & Seagar, M. (2000) · Biochimie · doi:10.1016/s0300-9084(00)00220-0 · Cited by 103 · see citing works
Receptor signalling and intracellular calcium in neutrophil activation
Lew, D. P. (1989) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1989.tb00240.x · Cited by 101 · see citing works
Self-citationKjeldsen, L., Bjerrum, O. W., Hovgaard, D., Johnsen, A. H., Sehested, M., & Borregaard, N. (1992) · European Journal Of Haematology · doi:10.1111/j.1600-0609.1992.tb00045.x · Cited by 98 · see citing works
Dahlgren, C., Carlsson, S. R., Karlsson, A., Lundqvist, H., & Sjölin, C. (1995) · Biochemical Journal · doi:10.1042/bj3110667 · Cited by 90 · see citing works
Self-citationBengtsson, T., Jaconi, M. E., Gustafson, M. B., Magnusson, K., Theler, J. M., Lew, D. P., & Stendahl, O. I. (1993) · PubMed · Cited by 87 · see citing works
Self-citationCalcium-dependent Oligomerization of Synaptotagmins I and II
Osborne, S. L., Herreros, J., Bastiaens, P., & Schiavo, G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.1.59 · Cited by 82 · see citing works
Membrane dynamics in phagocytosis
Booth, J. W., Trimble, W. S., & Grinstein, S. (2001) · Seminars in Immunology · doi:10.1006/smim.2001.0332 · Cited by 78 · see citing works
Nüße, O., Serrander, L., Lew, D. P., & Krause, K. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1279 · Cited by 64 · see citing works
Self-citation"In Vitro" Phosphorylation of Annexin 2 Heterotetramer by Protein Kinase C
Regnouf, F., Sagot, I., Delouche, B., Devilliers, G., Cartaud, J., Henry, J., & Pradel, L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.27143 · Cited by 59 · see citing works
Mollinedo, F., & Lazo, P. A. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6196 · Cited by 51 · see citing works
Calcium-dependent neutrophil secretion: characterization and regulation by annexins
Rosales, J. L., & Ernst, J. D. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.12.6195 · Cited by 48 · see citing works
Martı́n-Martı́n, B., Nabokina, S. M., Lazo, P. A., & Mollinedo, F. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.65.3.397 · Cited by 44 · see citing works
Intracellular Location of SNAP-25 in Human Neutrophils
Nabokina, S. M., Egea, G., Blasi, J., & Mollinedo, F. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7515 · Cited by 35 · see citing works
Baram, D., Michal Linial, B., Mekori, Y. A., & Sagi‐Eisenberg, R. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.10.5120 · Cited by 33 · see citing works
Ca2+-dependent exocytosis in mast cells is stimulated by the Ca2+ sensor, synaptotagmin I.
Baram, D., Linial, M., Mekori, Y. A., et al. (1998) · PubMed · Cited by 31 · see citing works
Differences in altered expression of L-selectin and Mac-1 in monocytes and neutrophils
Lundahl, J., & HED, J. (1994) · Inflammation · doi:10.1007/bf01534599 · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- L.A. Herzenberg, D.M. Weir, L.A. Herzenberg, C. Blackwell, Weir's Handbook of Experimental Immunology, vol. IV, 5th edn., Blackwell, Cambridge, MA, USA, 1996, pp. 159.1 -159.5.
- H. Sengelov, L. Kjeldsen, M.S. Diamond, T.A. Springer, N. Borre- gaard, J. Clin. Invest. 92 (1993) 1467 -1476.
- N. Borregaard, L. Kjeldsen, H. Sengelov, M.S. Diamond, T.A. Springer, H.C. Anderson, T.K. Kishimoto, D.F. Bainton, J. Leu- koc. Biol. 56 (1994) 80 -87.
Cited by
Sorted by citations
Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989 · see citing works
Lee, W. L., Harrison, R. E., & Grinstein, S. (2003) · Microbes and Infection · doi:10.1016/j.micinf.2003.09.014 · Cited by 433 · see citing works
Understanding exocytosis in immune and inflammatory cells: The molecular basis of mediator secretion
Logan, M. R., Odemuyiwa, S. O., & Moqbel, R. (2003) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(03)80114-8 · Cited by 155 · see citing works
Calcium signaling and regulation of neutrophil functions: Still a long way to go
Hann, J., Bueb, J., Tolle, F., & Bréchard, S. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ru0719-241r · Cited by 101 · see citing works
Ca2+ signalling early in evolution – all but primitive
Plattner, H., & Verkhratsky, A. (2013) · Journal of Cell Science · doi:10.1242/jcs.127449 · Cited by 58 · see citing works
Ladenburger, E., & Plattner, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027111 · Cited by 48 · see citing works
Lipid raft proteome of the human neutrophil azurophil granule
Feuk‐Lagerstedt, E., Movitz, C., Pellmé, S., Dahlgren, C., & Karlsson, A. (2006) · PROTEOMICS · doi:10.1002/pmic.200600482 · Cited by 47 · see citing works
Self-citationPlattner, H., Sehring, I. M., Mohamed, I. K., de Miranda, K. R., de Souza, W., Billington, R. A., Genazzani, A. A., & Ladenburger, E. (2012) · Cell Calcium · doi:10.1016/j.ceca.2012.01.006 · Cited by 46 · see citing works
The Exocytosis Regulator Synaptotagmin V Controls Phagocytosis in Macrophages
Vinet, A. F., Fukuda, M., & Descoteaux, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.8.5289 · Cited by 42 · see citing works
Involvement of Munc18 isoforms in the regulation of granule exocytosis in neutrophils
Brochetta, C., Vita, F., Tiwari, N., Scandiuzzi, L., Soranzo, M. R., Guérin-Marchand, C., Zabucchi, G., & Blank, U. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.05.023 · Cited by 41 · see citing works
The mast cell: where endocytosis and regulated exocytosis meet
Sagi‐Eisenberg, R. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00516.x · Cited by 41 · see citing works
Protein trafficking in immune cells
Benado, A., Nasagi-Atiya, Y., & Sagi‐Eisenberg, R. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.11.011 · Cited by 35 · see citing works
Expression and Function of Synaptotagmin VII in CTLs
Fowler, K. T., Andrews, N. W., & Huleatt, J. W. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.3.1498 · Cited by 32 · see citing works
Revisiting the role of calcium in phagosome formation and maturation
Westman, J., Grinstein, S., & Maxson, M. E. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr1118-444r · Cited by 31 · see citing works
Molecular Mechanisms of Calcium Signaling During Phagocytosis
Nunes, P., Kaba, M., & Demaurex, N. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-40406-2_7 · Cited by 20 · see citing works
Atiya-Nasagi, Y., Cohen, H., Medalia, O., Fukuda, M., & Sagi‐Eisenberg, R. (2005) · Journal of Cell Science · doi:10.1242/jcs.01710 · Cited by 15 · see citing works
Parrilla-Monge, L. (2015) · doi:10.14201/gredos.129646 · Cited by 13 · see citing works
Role of S100A8/A9 for Cytokine Secretion, Revealed in Neutrophils Derived from ER-Hoxb8 Progenitors
Zhou, Y., Hann, J., Schenten, V., Plançon, S., Bueb, J., Tolle, F., & Bréchard, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168845 · Cited by 11 · see citing works
Cytotoxic Granule Trafficking and Fusion in Synaptotagmin7-Deficient Cytotoxic T Lymphocytes
Sleiman, M., Stevens, D. R., Chitirala, P., & Rettig, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01080 · Cited by 10 · see citing works
Bacterial Endocytic Systems in Plants and Animals: Ca2+as a Common Theme?
Verhaert, J., Vanderleyden, J., & Michiels, J. J. (2005) · Critical Reviews in Plant Sciences · doi:10.1080/07352680500221054 · Cited by 7 · see citing works
Altered Calcium-Induced Exocytosis in Neutrophils from Allergic Patients
Liu, D., Zhang, J., Wu, J., Zhang, C., & Xu, T. (2004) · International Archives of Allergy and Immunology · doi:10.1159/000079165 · Cited by 5 · see citing works
Prognosis and immune function of Synaptotagmin-4 in gastric cancer and brain low-grade gliomaPreprint
Jiang, S., Zhu, L., Jiang, C. Q., Yu, S., Wang, B., & Ren, Y. T. (2020) · doi:10.21203/rs.3.rs-21652/v1 · Cited by 1 · see citing works
Prognostic and immune roles of synaptotagmin-4 in gastric cancer and brain lower-grade gliomaPreprint
Jiang, S., Zhu, L., Jiang, C. Y., Yu, S., Wang, B., & Ren, Y. T. (2020) · doi:10.21203/rs.3.rs-21652/v2 · Cited by 1 · see citing works
Zhao, L. (2004) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Lysosomes: How Plasma Membrane Repair Route Can Be Hijacked by Parasites?
Hissa, B., & Andrade, L. D. O. (2017) · InTech eBooks · doi:10.5772/intechopen.69305
Ca2+-Affinitive and Non-Ca2+-Affinitive Synaptotagmins in Human Pan-cancer
Wu, X., Gao, B., Xiao, K., & Saleem, N. (2025) · NeuroMolecular Medicine · doi:10.1007/s12017-025-08873-x
Ioannidis, M., den Ouden, M., Dijt, S. J., Incarnato, D., Grijpstra, P., Wortel, J., Verhage, M., Maassen, S., & van den Bogaart, G. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.24.690103
- Authors
- Lindmark, I. M., Karlsson, A., Serrander, L., Francois, P., Lew, D., Rasmusson, B., Stendahl, O., & Nüße, O.
- Affiliations
- University of Gothenburg (SE)
- University Hospital of Geneva (CH)
- Linköping University (SE)
- Université Henri Poincaré (FR)
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 1590
- Issue
- 1-3
- Pages
- 159-166
- ISSN
- 0167-4889 (ISSN-L)
- OpenAlex
- W2063808802
- Cited by
- 28
- References
- 44
- Citations by year
- 2025: 2 · 2021: 1 · 2020: 4 · 2019: 2 · 2017: 1 · 2015: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Swedish Foundation for International Cooperation in Research and Higher Education
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- synaptotagmin II, calcium sensing, neutrophils, phagocytosis, specific granules, exocytosis, phagolysosome fusion, complement receptor 3, LAMP1, fMLP stimulation, membrane translocation, calcium-dependent secretion
- MeSH terms
- Animals, Biological Transport, Active, Calcium, Cell Membrane, Exocytosis, Humans, Membrane Fusion, Membrane Glycoproteins, N-Formylmethionine Leucyl-Phenylalanine, Nerve Tissue Proteins, Neutrophils, Phagocytosis, Phagosomes, Subcellular Fractions, Antigens, CD, Rats, Sprague-Dawley, Synaptotagmin II, Rats, Lysosomal Membrane Proteins, In Vitro Techniques
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
