Syntaxin 6 and Vti1b Form a Novel SNARE Complex, Which Is Up-regulated in Activated Macrophages to Facilitate Exocytosis of Tumor Necrosis Factor-α
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A key function of activated macrophages is to secrete proinflammatory cytokines such as TNFalpha; however, the intracellular pathway and machinery responsible for cytokine trafficking and secretion is largely undefined. Here we show that individual SNARE proteins involved in vesicle docking and fusion are regulated at both gene and protein expression upon stimulation with the bacterial cell wall component lipopolysaccharide. Focusing on two intracellular SNARE proteins, Vti1b and syntaxin 6 (Stx6), we show that they are up-regulated in conjunction with increasing cytokine secretion in activated macrophages and that their levels are selectively titrated to accommodate the volume and timing of post-Golgi cytokine trafficking. In macrophages, Vti1b and syntaxin 6 are localized on intracellular membranes and are present on isolated Golgi membranes and on Golgi-derived TNFalpha vesicles budded in vitro. By immunoprecipitation, we find that Vti1b and syntaxin 6 interact to form a novel intracellular Q-SNARE complex. Functional studies using overexpression of full-length and truncated proteins show that both Vti1b and syntaxin 6 function and have rate-limiting roles in TNFalpha trafficking and secretion. This study shows how macrophages have uniquely adapted a novel Golgi-associated SNARE complex to accommodate their requirement for increased cytokine secretion.
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After synthesis in the ER, the SNARE proteins Stx6, Stx7, Vtib mediate the fusion of TNF-containing vesicles from the Golgi complex with VAMP3+-recycling endosomes.
“After synthesis in the ER, the SNARE proteins Stx6, Stx7, Vtib mediate the fusion of TNF-containing vesicles from the Golgi complex with VAMP3+-recycling endosomes (17, 19).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [19]
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 · see citing works
Pagan, J. K., Wylie, F. G., Joseph, S., Widberg, C., Bryant, N. J., James, D. E., & Stow, J. L. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00006-x · Cited by 130 · see citing works
Self-citationWade, N., Bryant, N. J., Connolly, L. M., Simpson, R. J., Luzio, J. P., Piper, R. C., & James, D. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010838200 · Cited by 89 · see citing works
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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
SNAREing immunity: the role of SNAREs in the immune system
Stow, J. L., Manderson, A. P., & Murray, R. Z. (2006) · Nature Reviews Immunology · doi:10.1038/nri1980 · Cited by 235 · see citing works
Self-citationIdentification of evolutionarily conserved gene networks mediating neurodegenerative dementia
Swarup, V., Hinz, F. I., Rexach, J. E., Noguchi, K.-I., Toyoshiba, H., Oda, A., Hirai, K., Sarkar, A., Seyfried, N. T., Cheng, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0223-3 · Cited by 136 · see citing works
Chaste, P., Klei, L., Sanders, S. J., Hus, V., Murtha, M. T., Lowe, J. K., Willsey, A. J., Moreno-De-Luca, D., Yu, T. W., Fombonne, E., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.09.017 · Cited by 144 · see citing works
Intracellular trafficking and secretion of inflammatory cytokines
Stow, J. L., & Murray, R. Z. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.04.001 · Cited by 128 · see citing works
Self-citationZhang, Y., Sun, Y., Rao, E., Yan, F., Li, Q., Zhang, Y., Silverstein, K. A. T., Liu, S., Sauter, E., Cleary, M. P., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2689 · Cited by 129 · see citing works
Han, C., Chen, T., Yang, M., Li, N., Liu, H., & Cao, X. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802002 · Cited by 56 · see citing works
- Authors
- Murray, R. Z., Wylie, F. G., Khromykh, T., Hume, D. A., & Stow, J. L.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Stow, Jennifer L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 280
- Issue
- 11
- Pages
- 10478-10483
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1985183555
- Cited by
- 157
- References
- 3
- Citations by year
- 2025: 2 · 2024: 11 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 8 · 2016: 7 · 2015: 7 · 2014: 10 · 2013: 8 · 2012: 17
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- syntaxin 6, Vti1b, SNARE complex, macrophage activation, TNF-α, cytokine production, exocytosis, Golgi apparatus, lipopolysaccharide, vesicle fusion, post-Golgi trafficking
- MeSH terms
- Animals, Carrier Proteins, Cell Line, Exocytosis, Golgi Apparatus, Inflammation, Lipopolysaccharides, Macrophages, Membrane Proteins, Microscopy, Fluorescence, RNA, Time Factors, Tumor Necrosis Factor-alpha, Immunoblotting, Up-Regulation, Cytokines, Oligonucleotide Array Sequence Analysis, Vesicular Transport Proteins, Immunoprecipitation, Green Fluorescent Proteins, SNARE Proteins, Qa-SNARE Proteins, Qb-SNARE Proteins, Mice
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