| Project/Area Number |
11670011
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Asahikawa Medical College (2000-2001)
Osaka University (1999) |
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Principal Investigator |
WATANABE Tsuyoshi Asahikawa Medical College, Dept. of Anatomy II, Professor, 医学部, 教授 (80220903)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Chromogranin / Secretogranin / Secretory granules / sorting mechanism / Yeast two hybrid system / endocrine cells / immunocyto chemistry / rat / セレクトグラニン / Yeast two hybrid法 / Yeast-two hybrid法 / グラニン蛋白群 / 蛋白選別輸送 / クロモグラニンA / セクレトグラニンIII / 免疫組織化学法 / セクレトグラニン / Yeast Two Hybrid / ペプチドホルモン / 蛋白間相互作用 |
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| Research Abstract |
Granins (chromogranins/secretogranins) are acidic secretory proteins which are specifically localized to secretory granules in various endocrine cells with peptide hormones. As we previously demonstrated, two representative granins, chromogranin A (CgA) and secretogranin II (SgII), are separately localized to two distinct subsets of secretory granules in rat pituitary gonadotropes, and the sizes and composition of secretory granules in gonadotropes are closely associated with the expression levels of these granins. Based on these findings it is suggested that granins function as fundamental matrices of secretory granules, although the targeting mechanisms of the granins for secretory granules still remain unexplained.
During attempts to discover the molecules responsible for the transport of granins to secretory granules, secretogranin III (SgIII), another member of the granin family, was identified as a binding partner of CgA with yeast two-hybrid screens and assays. The interaction between SgIII and CgA was augmented under low pH and high calcium conditions that mimic the luminal milieu at the trans-Golgi network. Immmunocytochemical analyzes demonstrated that both proteins were co-localized in secretory granules of endocrine cells in vivo , and that the deletion of the SgIII -binding domain of CgA impaired its targeting for secretory granules in AtT-20 cells. These findings suggest that SgIII acts as an interface molecule between CgA and a putative sorting receptor destined for secertory granules. These heterophilic complex of two or more granins might also contribute to the organization of secretory granules in general, by providing multiple anchor sites for both regulated secretory proteins and membrane-bound proteins such as processing enzymes, ion channels, amine transporters, and fusion machineries required for regulated exocytosis.
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