Granuphilin molecularly docks insulin granules to the fusion machinery
| العنوان: | Granuphilin molecularly docks insulin granules to the fusion machinery |
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| المؤلفون: | Kazuo Kasai, Shin Mizutani, Hiroshi Gomi, Tetsuro Izumi, Shigeyoshi Itohara |
| المصدر: | The Journal of Cell Biology |
| بيانات النشر: | Rockefeller University Press, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Models, Molecular, medicine.medical_treatment, Genetic Vectors, Mutant, Vesicular Transport Proteins, Biology, Membrane Fusion, Article, Exocytosis, Adenoviridae, Cell membrane, Islets of Langerhans, Mice, Insulin Secretion, medicine, Animals, Insulin, Secretion, RAB27, Research Articles, Mice, Knockout, Secretory Vesicles, Cell Membrane, Granule (cell biology), Gene Transfer Techniques, Lipid bilayer fusion, Cell Biology, Cell biology, Phenotype, medicine.anatomical_structure, Carrier Proteins |
| الوصف: | The Rab27a effector granuphilin is specifically localized on insulin granules and is involved in their exocytosis. Here we show that the number of insulin granules morphologically docked to the plasma membrane is markedly reduced in granuphilin-deficient β cells. Surprisingly, despite the docking defect, the exocytosis of insulin granules in response to a physiological glucose stimulus is significantly augmented, which results in increased glucose tolerance in granuphilin-null mice. The enhanced secretion in mutant β cells is correlated with a decrease in the formation of the fusion-incompetent syntaxin-1a–Munc18-1 complex, with which granuphilin normally interacts. Furthermore, in contrast to wild-type granuphilin, its mutant that is defective in binding to syntaxin-1a fails to restore granule docking or the protein level of syntaxin-1a in granuphilin-null β cells. Thus, granuphilin not only is essential for the docking of insulin granules but simultaneously imposes a fusion constraint on them through an interaction with the syntaxin-1a fusion machinery. These findings provide a novel paradigm for the docking machinery in regulated exocytosis. |
| تدمد: | 1540-8140 0021-9525 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2dabc1e729bbfd12c96db7e28cd222e https://doi.org/10.1083/jcb.200505179 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f2dabc1e729bbfd12c96db7e28cd222e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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