ArticleThe EMBO journal1997
The first C2 domain of synaptotagmin is required for exocytosis of insulin from pancreatic beta-cells: action of synaptotagmin at low micromolar calcium.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 111 citations in OpenAlex.
- Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.PLoS biology · 2023Article
- Type 2 diabetes candidate genes, including PAX5, cause impaired insulin secretion in human pancreatic islets.The Journal of clinical investigation · 2023Article
- The role of miRNAs in polycystic ovary syndrome with insulin resistance.Journal of assisted reproduction and genetics · 2021Review
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Triggered Ca2+ influx is required for extended synaptotagmin 1-induced ER-plasma membrane tethering.The EMBO journal · 2015Article
- Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome.Journal of assisted reproduction and genetics · 2014Article
- The functional significance of synaptotagmin diversity in neuroendocrine secretion.Frontiers in endocrinology · 2013Review
- Gene expression profiles in rat mesenteric lymph nodes upon supplementation with conjugated linoleic acid during gestation and suckling.BMC genomics · 2011Article
- Insulin granule biogenesis, trafficking and exocytosis.Vitamins and hormones · 2009Review
- Regulation of CFTR trafficking by its R domain.The Journal of biological chemistry · 2008Article
- The calcium-sensing protein synaptotagmin 7 is expressed on different endosomal compartments in endocrine, neuroendocrine cells or neurons but not on large dense core vesicles.Histochemistry and cell biology · 2007Article
- Distinct roles of the C2A and the C2B domain of the vesicular Ca2+ sensor synaptotagmin 9 in endocrine beta-cells.The Biochemical journal · 2007Article
- Protein kinase activation increases insulin secretion by sensitizing the secretory machinery to Ca2+.The Journal of general physiology · 2004Article
- RNA interference-mediated silencing of synaptotagmin IX, but not synaptotagmin I, inhibits dense-core vesicle exocytosis in PC12 cells.The Biochemical journal · 2004Article
- GABA in the endocrine pancreas: its putative role as an islet cell paracrine-signalling molecule.The Journal of general physiology · 2004Review
- Insulin granule dynamics in pancreatic beta cells.Diabetologia · 2003Review
- The C2A domain of synaptotagmin-like protein 3 (Slp3) is an atypical calcium-dependent phospholipid-binding machine: comparison with the C2A domain of synaptotagmin I.The Biochemical journal · 2002Article
- Characterization of KIAA1427 protein as an atypical synaptotagmin (Syt XIII).The Biochemical journal · 2001Article
- Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Synaptotagmin VII regulates Ca(2+)-dependent exocytosis of lysosomes in fibroblasts.The Journal of cell biology · 2000Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ca2+- and phospholipid-binding protein synaptotagmin is involved in neuroexocytosis. Its precise role and Ca2+-affinity in vivo are unclear. We investigated its putative function in insulin secretion which is maximally stimulated by 10 microM cytosolic free Ca2+. The well-characterized synaptotagmin isoforms I and II are present in pancreatic beta-cell lines RINm5F, INS-1 and HIT-T15 as shown by Northern and Western blots. Subcellular fractionation and confocal microscopy revealed their presence mainly on insulin-containing secretory granules whereas only minor amounts were found on synaptic vesicle-like microvesicles. Antibodies or Fab-fragments directed against the Ca2+-dependent phospholipid binding site of the first C2 domain of synaptotagmin I or II inhibited Ca2+-stimulated, but not GTPgammaS-induced exocytosis from streptolysin-O-permeabilized INS-1 and HIT-T15 cells. Transient expression of wild-type synaptotagmin II did not alter exocytosis in HIT-T15 cells. However, mutations in the Ca2+-dependent phospholipid binding site of the first C2 domain (Delta180-183, D231S) again inhibited only Ca2+-, but not GTPgammaS-evoked exocytosis. In contrast, mutations in the IP4-binding sites of the second C2 domain (Delta325-341; K327,328, 332Q) did not alter exocytosis. Synaptotagmin II mutated in both C2 domains (Delta180-183/K327,328,332Q) induced greater inhibition than mutant Delta180-183, suggesting a discrete requirement for the second C2 domain. Thus, synaptotagmin isoforms regulate exocytotic events occurring at low micromolar Ca2+.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.