ArticleThe Journal of biological chemistry2011
Munc18-1 and Munc18-2 proteins modulate beta-cell Ca2+ sensitivity and kinetics of insulin exocytosis differently.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Functional differences of Munc18 isoforms reflect their affinities for the exocytosis site.Cellular and molecular life sciences : CMLS · 2026Article
- Characteristics of Berberine Effects on Insulin Exocytosis in Pancreatic β Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- NMDA receptor inhibition increases, synchronizes, and stabilizes the collective pancreatic beta cell activity: Insights through multilayer network analysis.PLoS computational biology · 2021Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Collective Sensing of β-Cells Generates the Metabolic Code.Frontiers in physiology · 2018Article
- Bi-Allelic Mutations in STXBP2 Reveal a Complementary Role for STXBP1 in Cytotoxic Lymphocyte Killing.Frontiers in immunology · 2018Article
- Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta cells.Cell calcium · 2017Review
- Key proteins involved in insulin vesicle exocytosis and secretion.Biomedical reports · 2017Article
- Article
- Munc18-2 is required for Syntaxin 11 Localization on the Plasma Membrane in Cytotoxic T-Lymphocytes.Traffic (Copenhagen, Denmark) · 2015Article
- Dual Opposing Roles of Metallothionein Overexpression in C57BL/6J Mouse Pancreatic β-Cells.PloS one · 2015Article
- Doc2b enrichment enhances glucose homeostasis in mice via potentiation of insulin secretion and peripheral insulin sensitivity.Diabetologia · 2014Article
- Article
- Multiple roles for the actin cytoskeleton during regulated exocytosis.Cellular and molecular life sciences : CMLS · 2013Review
- Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells.Diabetologia · 2013Article
- Doc2b is a key effector of insulin secretion and skeletal muscle insulin sensitivity.Diabetes · 2012Article
- Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms.The Journal of biological chemistry · 2012Article
- Deploying insulin granule-granule fusion to rescue deficient insulin secretion in diabetes.Diabetologia · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fast neurotransmission and slower hormone release share the same core fusion machinery consisting of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins. In evoked neurotransmission, interactions between SNAREs and the Munc18-1 protein, a member of the Sec1/Munc18 (SM) protein family, are essential for exocytosis, whereas other SM proteins are dispensable. To address if the exclusivity of Munc18-1 demonstrated in neuroexocytosis also applied to fast insulin secretion, we characterized the presence and function of Munc18-1 and its closest homologue Munc18-2 in β-cell stimulus-secretion coupling. We show that pancreatic β-cells express both Munc18-1 and Munc18-2. The two Munc18 homologues exhibit different subcellular localization, and only Munc18-1 redistributes in response to glucose stimulation. However, both Munc18-1 and Munc18-2 augment glucose-stimulated hormone release. Ramp-like photorelease of caged Ca(2+) and high resolution whole-cell patch clamp recordings show that Munc18-1 and Munc18-2 overexpression shift the Ca(2+) sensitivity of the fastest phase of insulin exocytosis differently. In addition, we reveal that Ca(2+) sensitivity of exocytosis in β-cells depends on the phosphorylation status of the Munc18 proteins. Even though Munc18-1 emerges as the key SM-protein determining the Ca(2+) threshold for triggering secretory activity in a stimulated β-cell, Munc18-2 has the ability to increase Ca(2+) sensitivity and thus mediates the release of fusion-competent granules requiring a lower cytoplasmic-free Ca(2+) concentration, [Ca(2+)](i)(.) Hence, Munc18-1 and Munc18-2 display distinct subcellular compartmentalization and can coordinate the insulin exocytotic process differently as a consequence of the actual [Ca(2+)](i).
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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.