Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells
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Aims/hypothesis The molecular basis of the exocytosis of secretory insulin-containing granules (SGs) during biphasic glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells remains unclear. Syntaxin (SYN)-1A and SYN-4 have been shown to mediate insulin exocytosis. The insulin-secretory function of SYN-3, which is particularly abundant in SGs, is unclear.Methods Mouse pancreatic islets and INS-1 cells were treated with adenovirus carrying Syn-3 (also known as Stx3) or small interfering RNA targeting Syn-3 in order to examine insulin secretion by radioimmunoassay. The localisation and distribution of insulin granules were examined by confocal and electron microscopy. Dynamic single-granule fusion events were assessed using total internal reflection fluorescence microscopy (TIRFM).Results Depletion of endogenous SYN-3 inhibited insulin release. TIRFM showed no change in the number or fusion competence of previously docked SGs but, instead, a marked reduction in the recruitment of newcomer SGs and their subsequent exocytotic fusion during biphasic GSIS. Conversely, overexpression of Syn-3 enhanced both phases of GSIS, owing to the increase in newcomer SGs and, remarkably, to increased SG-SG fusion, which was confirmed by electron microscopy.Conclusions/interpretation In insulin secretion, SYN-3 plays a role in the mediation of newcomer SG exocytosis and SG-SG fusion that contributes to biphasic GSIS.
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Numerous SNARE isoforms, including syntaxin-1, -3 and -4, SNAP-25 and -23, and VAMP2 and -3, are involved in glucose-stimulated insulin secretion, whereas VAMP8 is non-essential for glucose-stimulated insulin secretion but has a role in GLP-1-potentiated insulin secretion.
“To date, numerous SNARE isoforms, including syntaxin-1, -3 and -4, SNAP-25 and -23, as well as syntaptobrevins 2 and 3 (VAMP2 and 3), have been shown to be involved in glucose-stimulated insulin secretion,42, 43, 44, 45, 46 whereas VAMP8, a non-essential SNARE protein for glucose-stimulated insulin secretion, has a role in the regulation of the glucagon-like peptide-1-potentiated insulin secretion”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [46]
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Experimental — accuracy not yet measuredUnlike syntaxin-1, syntaxin-3 localizes to secretory granules and is involved in the release of newcomer granules.
“Unlike syntaxin-1, syntaxin-3 localizes to the secretory granules. It is involved in the release of newcomer granules (769).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [769]
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- Authors
- Zhu, D., Koo, E., Kwan, E., Kang, Y., Park, S., Xie, H., Sugita, S., & Gaisano, H. Y.
- Affiliations
- University of Toronto (CA)
- University Health Network (CA)
- Corresponding author
- Gaisano, H. Y.
- Venue
- Diabetologia
- Published
- 2012-11-07
- Volume
- 56
- Issue
- 2
- Pages
- 359-369
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2005270516
- Cited by
- 81
- References
- 46
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 11 · 2016: 6 · 2015: 8 · 2014: 9 · 2013: 4 · 2012: 2
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Toronto
- Canadian Institutes of Health Research (MOP86544, MOP89889)
- Banting and Best Diabetes Centre, University of Toronto
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- syntaxin 3, insulin granules, exocytosis, pancreatic beta cells, insulin secretion, granule docking, INS-1 cells, islets
- MeSH terms
- Insulin Secretion, Animals, Cell Line, Exocytosis, Humans, Insulin, Islets of Langerhans, Microscopy, Electron, Microscopy, Fluorescence, Radioimmunoassay, Blotting, Western, Microscopy, Confocal, RNA, Small Interfering, Insulin-Secreting Cells, Qa-SNARE Proteins, Mice
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