The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.
The t-SNARE Syntaxin 4 Is Regulated during Macrophage Activation to Function in Membrane Traffic and Cytokine Secretion
Open accessAbstract
Activation of macrophages with lipopolysaccharide (LPS) induces the rapid synthesis and secretion of proinflammatory cytokines, such as tumor necrosis factor (TNFalpha), for priming the immune response. TNFalpha plays a key role in inflammatory disease; yet, little is known of the intracellular trafficking events leading to its secretion. In order to identify molecules involved in this secretory pathway, we asked whether any of the known trafficking proteins are regulated by LPS. We found that the levels of SNARE proteins were rapidly and significantly up- or downregulated during macrophage activation. A subset of t-SNAREs (Syntaxin 4/SNAP23/Munc18c) known to control regulated exocytosis in other cell types was substantially increased by LPS in a temporal pattern coinciding with peak TNFalpha secretion. Syntaxin 4 formed a complex with Munc18c at the cell surface of macrophages. Functional studies involving the introduction of Syntaxin 4 cDNA or peptides into macrophages implicate this t-SNARE in a rate-limiting step of TNFalpha secretion and in membrane ruffling during macrophage activation. We conclude that, in macrophages, SNAREs are regulated in order to accommodate the rapid onset of cytokine secretion and for membrane traffic associated with the phenotypic changes of immune activation. This represents a novel regulatory role for SNAREs in regulated secretion and in macrophage-mediated host defense.
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In the citing paper
“In macrophages, TNF is released to the extracellular milieu via the constitutive secretion pathway, and its trafficking is the best understood of all cytokines (9, 17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [18]
In the citing paper
“Thence, the Stx4/SNAP23/VAMP3 complex facilitates the passage of TNF from recycling endosomes to the cell membrane (17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [18]
In the citing paper
“Moreover, LPS was found to increase the expression of vesicle trafficking proteins that regulate TNF trafficking (17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [18]
In the citing paper
“The post-Golgi trafficking of IL-6 follows a route that is also dependent on Stx6 and Vti1b, which form a complex with cognate SNARE VAMP3 at recycling endosomes (17, 18).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [18]
Citations
Cites
A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells
Black, R. A., Rauch, C. T., Kozlosky, C. J., Peschon, J. J., Slack, J. L., Wolfson, M. F., Castner, B. J., Stocking, K. L., Reddy, P., Srinivasan, S., et al. (1997) · Nature · doi:10.1038/385729a0 · Cited by 3,149
Toll-like receptors in the induction of the innate immune response
Aderem, A. A., & Ulevitch, R. J. (2000) · Nature · doi:10.1038/35021228 · Cited by 3,082
Mellman, I., & Steinman, R. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00449-4 · Cited by 2,256
The Pathophysiology of Tumor Necrosis Factors
VASSALLI, P. (1992) · Annual Review of Immunology · doi:10.1146/annurev.iy.10.040192.002211 · Cited by 1,874
Origin, maturation and antigen presenting function of dendritic cells
Cella, M., Sallusto, F., & Lanzavecchia, A. (1997) · Current Opinion in Immunology · doi:10.1016/s0952-7915(97)80153-7 · Cited by 1,339
Regulated transport of the glucose transporter GLUT4
Bryant, N. J., Govers, R., & James, D. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm782 · Cited by 1,183
Self-citationSNARE-mediated membrane fusion
Chen, Y. A., & Scheller, R. H. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052017 · Cited by 1,133
Araki, N., Johnson, M. T., & Swanson, J. A. (1996) · The Journal of cell biology · doi:10.1083/jcb.135.5.1249 · Cited by 949
Protein-Protein Interactions Contributing to the Specificity of Intracellular Vesicular Trafficking
Calakos, N., Bennett, M. K., Peterson, K. E., & Scheller, R. H. (1994) · Science · doi:10.1126/science.8108733 · Cited by 399
Guo, Z., Turner, C., & Castle, D. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81594-9 · Cited by 254
Research works printed but not linked: 1
- Hackam, 1996, Characterization and subcellular localization of target membrane soluble NSF attachment protein receptors (t-SNAREs) in macrophages, Syntaxins, 2
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
“Thence, the Stx4/SNAP23/VAMP3 complex facilitates the passage of TNF from recycling endosomes to the cell membrane (17, 18).”
BackgroundInfluentialHong, W. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2005.03.014 · Cited by 648
“Syn4 has also been implicated in lipopolysaccharide (LPS)-induced secretion of tumor necrosis factor (TNF) in macrophages [142].”
BackgroundT cells use two directionally distinct pathways for cytokine secretion
Huse, M., Lillemeier, B. F., Kuhns, M. S., Chen, D. S., & Davis, M. M. (2006) · Nature Immunology · doi:10.1038/ni1304 · Cited by 436
“A similar strategy has been used before to assess TNF secretion from macrophage”
MethodCytokine release from innate immune cells: association with diverse membrane trafficking pathways
Lacy, P., & Stow, J. L. (2011) · Blood · doi:10.1182/blood-2010-08-265892 · Cited by 426
Self-citationThe macrophage response towards LPS and its control through the p38MAPK–STAT3 axis
Bode, J. G., Ehlting, C., & Häussinger, D. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.018 · Cited by 397
Metadata
- Authors
- Pagan, J. K., Wylie, F. G., Joseph, S., Widberg, C., Bryant, N. J., James, D. E., & Stow, J. L.
- Affiliations
- The University of Queensland (AU)
- Institute for Molecular Bioscience (AU)
- Garvan Institute of Medical Research (AU)
- Corresponding author
- Stow, Jennifer L
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 13
- Issue
- 2
- Pages
- 156-160
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2155132039
- Cited by
- 130
- References
- 28
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 11 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 9 · 2014: 8 · 2013: 7 · 2012: 7
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3850 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- syntaxin 4, macrophage activation, lipopolysaccharide, TNF-alpha secretion, regulated exocytosis, membrane traffic, Munc18c, SNAP23, cytokine production, ruffles
- MeSH terms
- Animals, Cell Line, Cell Membrane, Lipopolysaccharides, Macrophage Activation, Membrane Proteins, Tumor Necrosis Factor-alpha, Cytokines, Vesicular Transport Proteins, SNARE Proteins, Qa-SNARE Proteins, Mice
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