2000 Fiscal Year Final Research Report Summary
The mechanisms of insulin-regulated exocytosis of the GLUT4-containing vesicles
| Project/Area Number |
11671107
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Gunma University, Institute For Molecular and Cellular Regulation |
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Principal Investigator |
SHIBATA Hiroshi Institute for Molecular and Cellular Regulation, , Gunma University, Department of Cell Biology, Associate Professor, 生体調節研究所, 助教授 (20235584)
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| Project Period (FY) |
1999 – 2000
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| Keywords | insulin / glucose transporter / GTP-binding protein / Rab4 / syntaxin4 / SNARE |
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| Research Abstract |
In the present study, we investigated the interaction of Rab4 with syntaxin4, a t-SNARE protein implicated in the insulin-induced exocytic fusion of the GLUT4-containing vesicle with the plasma membrane. Rab4 and syntaxin4 were coimmunoprecipitated from the lysates of rat adipocytes. The interaction of the two proteins were attenuated by pretreatment of the cells with insulin but enhanced with GTPgS.A GTPase deficient mutant of Rab4, but not a GTP-binding defective mutant was bound to syntaxin 4, suggesting that the interaction between the two proteins were regulated by the guanine-nucleotide-binding state of Rab4. In addition, we found that the presence of munc-18c, a negative regulator of the SNARE comple formation, displaced Rab4 from syntaxin 4, indicating that the dissociation of munc-18c from syntaxin4 is required for Rab4 to bind to syntaxin 4.
We also clarified that the actin filaments play a critical role in exocytotic recruitment but not in endocytosis of GLUT4 in isolated rat adipocytes.
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[Publications] Suzuki, J., Ohnishi, H., Shibata, H., Iiri, T., Wada, A., Hirayama, T., Ueda, N., Kanamatsu, C., Tsuchida, T., Mashima, H., Yasuda, H.and Fujita, T.: "Dynamin is involved jin the vacuolation induced by Helicobacter Pylori vacuolating cytotoxin (VacA)."J.Clin.Invest.. 107. 363-370 (2001)
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[Publications] Kanzaki, M., Zhang, Y.-Q., Mashima, H., Li, L., Shibata, H.and Kojima, I.: "Transloacation of a calcium-permeable channel induced by insulin-like growth factor-I."Nature Cell Biol.. 1. 165-170 (1999)
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[Publications] Ohnishi, H., Mine, T., Shibata, H., Ueda, N., Tsuchida, T., and Fujita, T.: "Involvement of Rab4 in regulated exocytosis of rat pancreatic acini."Gastroenterology. 116. 943-952 (1999)
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「研究成果報告書概要(欧文)」より
