Docking and fusion of insulin granules
| Project/Area Number |
18390269
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
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Principal Investigator |
IZUMI Tetsuro Gunma University, Institute for Molecular and Cellular Regulation, Department of Molecular Medicine, Professor (00212952)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,260,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2006: ¥10,500,000 (Direct Cost: ¥10,500,000)
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| Keywords | insulin / secretory granules / exocytosis / docking / total internal reflection fluorescence microscopy / 分泌穎粒 / 細胞膜 / 膜融合 |
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| Research Abstract |
We examined secretory granule dynamics using total internal reflection fluorescence microscopy in normal pancreatic beta cells and their mutants devoid of Rab27a and/or its effector, granuphilin, which play critical roles in the docking and recruitment of insulin granules to the plasma membrane. In the early phase of glucose stimulation in wild-type cells, we observed marked fusion of granules recruited from a relatively distant area, in parallel with that from granules located underneath the plasma membrane. Furthermore, despite a lack of granules directly attached to the plasma membrane, both spontaneous and evoked fusion was increased in granuphilin-null cells. In addition to these granuphilin-null phenotypes, Rab27a/granuphilin doubly deficient cells showed the decreases in granules located next to the docked area and in fusion from granules near the plasma membrane in the early phase of glucose-stimulated secretion, similar to Rab27a-mutated cells. Thus, the two proteins play non-overlapping roles in insulin exocytosis: granuphilin acts on the granules underneath the plasma membrane, whereas Rab27a acts on those in a more distal area. These findings demonstrate that, in contrast to our conventional understanding, stable attachment of secretory granules to the plasma membrane is not prerequisite but temporally inhibitory for both spontaneous and evoked fusion.
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Report
(3 results)
Research Products
(68 results)
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[Journal Article] Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice2006
Author(s)
Kato T, Shimano H, Yamamoto T, Yokoo T, Endo Y, Ishikawa M, Matsuzaka T, Nakagawa Y, Kumadaki S, Yahagi N, Takahashi A, Sone H, Suzuki H, Toyoshima H, Hasty AH, Takahashi S, Gomi H, Izumi T, and Yamada N
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Journal Title
Cell Metab. 4
Pages: 143-154
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice2006
Author(s)
Kato T, Shimano H, Yamamoto T, Yokoo T, Endo Y, Ishikawa M, Matsuzaka T, Nakagawa Y, Kumadaki S, Yahagi N, Takahashi A, Sone H, Suzuki H, Toyoshima H, Hasty AH, Takahashi S, Gomi H, Izumi T, and Yamada N.
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Journal Title
Cell Metab 4
Pages: 143-154
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Rab27b structure swaps under GDP binding2006
Author(s)
Leonard MG Chavas, Seiji Torii, Hlronari Kamikubo, Masato Kawasaki, Kentaro Ihara, Ryuichi Kato, Mikio Kataoka, Tetsuro Izumi, Soichi Wakatsuki.
Organizer
Joint Conference of the Asian Crystallographic association and the Crystallographic Society in Japan
Place of Presentation
Tsukuba, Japan
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] Are urothelial fusiform vesicles lysosome-related organelles?2006
Author(s)
Xuemei Guo, Iwona Gumper, Heide Plesken, Edward K. Novak, Sreenivasulu Chintala, Richard T. Swank, Tetsuro Izumi, Tung-Tien Sun, David D. Sabatini, and Gert Kreibich
Organizer
46th annual meeting, the American Society for Cell Biology
Place of Presentation
San. Diego, California, USA
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] Rab27b st ructure swaps under GDP binding2006
Author(s)
Leonard MG Chavas, Seiji Torii, HIronari Kamikubo, Masato Kawasaki, Kentaro Ihara, Ryuichi Kato, Mikio Kataoka, Tetsuro Izumi, Soichi Wakatsuki.
Organizer
Joint Conference of the Asian Crystallographic association and the Crystallographic Society in Japan
Place of Presentation
Tsukuba, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Are Urothelial Fusiform Vesicles Lysosome-Related Organelles2006
Author(s)
Xuemei Guo, Iwona Gumper, Heide Plesken, Edward K. Novak, Sreenivasulu Chintala, Richard T. Swank, Tetsuro Izumi, Tung-Tien Sun, David D. Sabatini, and Gert Kreibich.
Organizer
46th annual meeting, the American Society for Cell Biology
Place of Presentation
San Diego, California, USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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