ArticleDiabetes2009
DOC2B: a novel syntaxin-4 binding protein mediating insulin-regulated GLUT4 vesicle fusion in adipocytes.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction.Cell communication and signaling : CCS · 2025Article
- Role of ghrelin hormone in the development of alcohol-associated liver disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Pancreatic β-cells package double C2-like domain beta protein into extracellular vesicles via tandem C2 domains.Frontiers in endocrinology · 2024Article
- SNARE-binding protein synaptosomal-associated protein of 29 kDa (SNAP29) regulates the intracellular sequestration of glucose transporter 4 (GLUT4) vesicles in adipocytes.Journal of diabetes investigation · 2023Article
- GLUT4 On the move.The Biochemical journal · 2022Article
- Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.Frontiers in endocrinology · 2022Review
- Doc2 Proteins Are Not Required for the Increased Spontaneous Release Rate in Synaptotagmin-1-Deficient Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- DOC2B promotes insulin sensitivity in mice via a novel KLC1-dependent mechanism in skeletal muscle.Diabetologia · 2019Article
- Protein kinase C iota facilitates insulin-induced glucose transport by phosphorylation of soluble nSF attachment protein receptor regulator (SNARE) double C2 domain protein b.Journal of diabetes investigation · 2019Article
- Cardiac SNARE Expression in Health and Disease.Frontiers in endocrinology · 2019Article
- The cell biology of systemic insulin function.The Journal of cell biology · 2018Review
- Article
- Phosphatidylinositol (4, 5)-bisphosphate targets double C2 domain protein B to the plasma membrane.Traffic (Copenhagen, Denmark) · 2017Article
- Exocytosis proteins as novel targets for diabetes prevention and/or remediation?American journal of physiology. Regulatory, integrative and comparative physiology · 2017Review
- Promoting Glucose Transporter-4 Vesicle Trafficking along Cytoskeletal Tracks: PAK-Ing Them Out.Frontiers in endocrinology · 2017Review
- Tctex1d2 Is a Negative Regulator of GLUT4 Translocation and Glucose Uptake.Endocrinology · 2015Article
- Structural elements that underlie Doc2β function during asynchronous synaptic transmission.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Insulin regulates Rab3-Noc2 complex dissociation to promote GLUT4 translocation in rat adipocytes.Diabetologia · 2015Article
- Munc18c: a controversial regulator of peripheral insulin action.Trends in endocrinology and metabolism: TEM · 2014Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveInsulin stimulates glucose uptake in skeletal muscle and adipose tissues primarily by stimulating the translocation of vesicles containing a facilitative glucose transporter, GLUT4, from intracellular compartments to the plasma membrane. The formation of stable soluble N-ethyl-maleimide-sensitive fusion protein [NSF] attachment protein receptor (SNARE) complexes between vesicle-associated membrane protein-2 (VAMP-2) and syntaxin-4 initiates GLUT4 vesicle docking and fusion processes. Additional factors such as munc18c and tomosyn were reported to be negative regulators of the SNARE complex assembly involved in GLUT4 vesicle fusion. However, despite numerous investigations, the positive regulators have not been adequately clarified. RESEARCH DESIGN AND
methodsWe determined the intracellular localization of DOC2b by confocal immunoflorescent microscopy in 3T3-L1 adipocytes. Interaction between DOC2b and syntaxin-4 was assessed by the yeast two-hybrid screening system, immunoprecipitation, and in vitro glutathione S-transferase (GST) pull-down experiments. Cell surface externalization of GLUT4 and glucose uptake were measured in the cells expressing DOC2b constructs or silencing DOC2b.
resultsHerein, we show that DOC2b, a SNARE-related protein containing double C2 domains but lacking a transmembrane region, is translocated to the plasma membrane upon insulin stimulation and directly associates with syntaxin-4 in an intracellular Ca(2+)-dependent manner. Furthermore, this process is essential for triggering GLUT4 vesicle fusion. Expression of DOC2b in cultured adipocytes enhanced, while expression of the Ca(2+)-interacting domain mutant DCO2b or knockdown of DOC2b inhibited, insulin-stimulated glucose uptake.
conclusionsThese findings indicate that DOC2b is a positive SNARE regulator for GLUT4 vesicle fusion and mediates insulin-stimulated glucose transport in adipocytes.
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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.