Human SCAMP5, a novel secretory carrier membrane protein, facilitates calcium-triggered cytokine secretion by interaction with snare machinery
Open accessAbstract
Cytokines produced by immune cells play pivotal roles in the regulation of both innate and adaptive immunity. However, the mechanisms controlling secretion of cytokines have not been fully elucidated. Secretory carrier membrane proteins (SCAMPs) are widely distributed integral membrane molecules implicated in regulating vesicular transport. In this study, we report the functional characterization of human SCAMP5 (hSCAMP5), a novel SCAMP protein that is widely expressed by a variety of neuronal and nonneuronal tissues and cells. By measuring the cytokine secretion (RANTES/CCL5 and IL-1beta) as an exocytotic model, we show that hSCAMP5 can promote the calcium-regulated signal peptide-containing cytokine (CCL5 but not IL-1beta) secretion in human epithelial cancer cells, human monocytes, and mouse macrophages. By using subcellular fractionation, immunofluorescence confocal microscopy, and membrane vesicle immunoisolation methods, we find that hSCAMP5 is mainly localized in the Golgi-associated compartments, and the calcium ionophore ionomycin can trigger a rapid translocation of hSCAMP5 from Golgi apparatus to plasma membrane along the classical exocytosis pathway. During the translocation of hSCAMP5 from Golgi apparatus to plasma membrane, hSCAMP5 can codistribute and complex with local soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) molecules. We further demonstrate that hSCAMP5 can directly interact with the calcium sensor synaptotagmins via the cytosolic C-terminal tail of hSCAMP5, thus providing a potential molecular mechanism linking SCAMPs with the SNARE molecules. Our findings suggest that hSCAMP5, in cooperation with the SNARE machinery, is involved in calcium-regulated exocytosis of signal peptide-containing cytokines.
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Stimulation of macrophages with ionomycin induces SCAMP5 translocation to the plasma membrane, where it colocalizes and interacts with Syt I and II, which mediate interactions with various SNAREs.
“Stimulation of macrophages with ionomycin induces SCAMP5 translocation to the plasma membrane, where it colocalizes and interacts with Syt I and II, which in turn mediate interactions with various SNAREs (77).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [77]
SCAMP5 governs post-Golgi trafficking of CCL5 to the plasmalemma.
“The secretory carrier membrane protein (SCAMP)5, a recycling endosome-associated protein, governs post-Golgi trafficking of CCL5 to the plasmalemma.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [77]
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Investigations into SCAMP5, a candidate lupus risk gene expressed in plasmacytoid dendritic cells
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Self-citationModulating the Tumor Microenvironment
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- Authors
- Han, C., Chen, T., Yang, M., Li, N., Liu, H., & Cao, X.
- Affiliations
- Tsinghua University (CN)
- Second Military Medical University (CN)
- Corresponding author
- Han, Chaofeng
- Cao, Xuetao
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-03-01
- Volume
- 182
- Issue
- 5
- Pages
- 2986-2996
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2116033937
- Cited by
- 56
- References
- 56
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 4 · 2019: 2 · 2018: 3 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 4
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30572122)
- 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 › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- SNARE proteins, calcium-triggered exocytosis, cytokine production, CCL5/RANTES, IL-1β, synaptotagmin, Golgi apparatus, ionomycin, macrophages, monocytes, epithelial cancer cells
- MeSH terms
- Calcium, Carrier Proteins, Cell Line, Exocytosis, HeLa Cells, Humans, Membrane Proteins, Receptors, Cell Surface, Signal Transduction, Cytokines, Protein Sorting Signals, Secretory Vesicles, SNARE Proteins
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