2004 Fiscal Year Final Research Report Summary
Signaling mechanism of epithelial cell-cell attachment and cell polarity.
| 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)
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| Project Period (FY) |
2000 – 2004
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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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[Journal Article] aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity.2004
Author(s)
Suzuki A, Hirata M, Kamimura K, Maniwa R, Yamanaka T, Mizuno K, Kishikawa M, Hirose H, Amano Y, Izumi N, Miwa Y, Ohno S.
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Journal Title
Curr Biology 14(16)
Pages: 1425-1435
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Phosphorylation of hUPF1 Induces Formation of mRNA Surveillance Complexes Containing hSMG-5 and hSMG-7.2003
Author(s)
Ohnishi, T., Yamashita, A, Matthias W., Hentze, M.W., Anderson, P., Ohno, S
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Journal Title
Molecular Cell 12(5)
Pages: 1187-1200
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Self-association of PAR-3 mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions.2003
Author(s)
Mizuno, K., Suzuki, A., Hirose, T., Kitamura, K., Kutsuzawa, Y., Amano, Y., Ohno, S.
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Journal Title
J. Biol. Chem. 278(33)
Pages: 31240-31250
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Phosphorylation of hUPF1 Induces Formation of mRNA Surveillance Complexes Containing hSMG-5 and hSMG-7.2003
Author(s)
Ohnishi, T., Yamashita, A., Kashima, I., Schell, T., Anders, K.R., Grimson, A., Hachiya, T., Matthias W.Hentze, M.W., Anderson, P., Ohno, S.
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Journal Title
Molecular Cell 12(5)
Pages: 1187-200
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Self-association of PAR-3 mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions.2003
Author(s)
Mizuno, K., Suzuki, A., Hirose, T., Kitamura, K., Kutsuzawa, Y., Futaki, M., Amano, Y., Ohno, S.
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Journal Title
J. Biol. Chem. 278(33)
Pages: 31240-31250
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mammalian Lg1 forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity.2003
Author(s)
Yamanaka, T., Horikoshi, Y., Sugiyama, Y., Ishiyama, C., Suzuki, A., Hirose, T., Iwamatsut, A., Shinohara, A., Ohno, S.
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Journal Title
Current Biology 13
Pages: 734-743
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarizatioin.2002
Author(s)
Suzuki, A., Ishiyama, C., Hashiba, K., Shimizu, M., Ebnet, K., Takai, Y., Ohno, S
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Journal Title
J.Cell Science 115
Pages: 3565-3573
Description
「研究成果報告書概要(和文)」より
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[Journal Article] aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization.2002
Author(s)
Suzuki, A., Ishiyama, C., Hashiba, K., Shimizu, M., Ebnet, K., Takai, Y.Ohno, S.
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Journal Title
J. Cell Science 115
Pages: 3565-3573
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] K-I. : Increased proliferation of B cells and auto-immunity in mice lacking protein kinase C delta.2002
Author(s)
Miyamoto, A., Nakayama, K., Imaki, H., Hirose, S., Jiang, Y., Abe, M., Tsukiyama, T., Nagahama, H., Ohno, S., Hatakeyama, S., Nakayama
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Journal Title
Nature 416
Pages: 865-869
Description
「研究成果報告書概要(欧文)」より
