Granuphilin molecularly docks insulin granules to the fusion machinery
| Autor: | Kazuo Kasai, Shin Mizutani, Hiroshi Gomi, Tetsuro Izumi, Shigeyoshi Itohara |
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| Rok vydání: | 2005 |
| Předmět: |
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 |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200505179 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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