| Project/Area Number |
12219215
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Yokohama City University |
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Principal Investigator |
OHNO Shigeo Yokohama City University, School of Medicine, Professor, 大学院医学研究科, 教授 (10142027)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Atsushi Yokohama City University, School of Medicine, Lecturer, 大学院医学研究科, 講師 (00264606)
MIZUNO Keiko Yokohama City University, School of Medicine, Assistant Professor, 医学部, 助手 (90221803)
AKIMOTO Kazunori Yokohama City University, School of Medicine, Assistant Professor, 医学部, 助手 (70285104)
杉山 由樹 横浜市立大学, 医学部, 日本学術振興会特別研究員
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥269,200,000 (Direct Cost: ¥269,200,000)
Fiscal Year 2004: ¥60,000,000 (Direct Cost: ¥60,000,000)
Fiscal Year 2003: ¥60,000,000 (Direct Cost: ¥60,000,000)
Fiscal Year 2002: ¥58,000,000 (Direct Cost: ¥58,000,000)
Fiscal Year 2001: ¥54,000,000 (Direct Cost: ¥54,000,000)
Fiscal Year 2000: ¥37,200,000 (Direct Cost: ¥37,200,000)
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| Keywords | aPKC / ASIP / PAR-3 / PAR-6 / Lg1 / Asymmetric division / cell polarity / epithelia |
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| Research Abstract |
Epithelial cells represent the fundamental cell type in metazoa, which constitute sheets covering surface and make boundary between the interior and exterior of the organism. They not only work as selective permeability barriers, but also play active physiological roles such as adsorption and secretion. Furthermore, they provide driving forces of dynamic morphogenesis for development through the considerable plasticity in their structural organization. Recent progress in understanding evolutionarily-conserved cell polarity-machinery has provided significant insight in the mechanism by which the epithelial apico-basal polarity is generated. The breakthrough was opened by genetic analysis in C.elegans, that found the presence of cell polarity proteins, PAR proteins (PAR-1 to PAR-6), which, are essential to establish anterior-posterior (A-P) polarity of the embryo. We found that, among these PAR proteins, PAR-3 and PAR-6 form a ternary complex with atypical PKC (aPKC) and works as core cassette in generating asymmetries in many different cell types of various species. In epithelia, the protein complex asymmetrically localize to apical membrane in Drosophila or TJ in cultured epithelial cells of mammals, and exert indispensable roles to develop epithelia-specific cell adhesion structures triggered by cell-cell contact. We also found that Lg1, another conserved polarity protein, is one of the downstream targets of aPKC/PAR-3/PAR-6 complex required to direct cell polarization of epithelial cells. We also demonstrate that, PAR-1b, plays a role on development of asymmetric membrane domains whereas it does not play a significant role on the formation of cell-cell junctions. aPKC excludes PAR-1b from the apical membrane in cooperation with 14-3-3, and thus antagonizes PAR-1b activity. Taken together, mammalian PAR-1b plays a role on the establishment and maintenance of epithelial cell polarity under the negative control of aPKC.
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