Mechanisms of formation of cell-cell junctions

• Project/Area Number: 15390099
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kumamoto University
• Principal Investigator: NAKANISHI Hiroyuki Kumamoto University, Graduate School of Medical Sciences, Professor, 大学院・医学薬学研究部, 教授 (80314318)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥13,400,000 (Direct Cost: ¥13,400,000); Fiscal Year 2004: ¥5,100,000 (Direct Cost: ¥5,100,000); Fiscal Year 2003: ¥8,300,000 (Direct Cost: ¥8,300,000)
• Keywords: cell-cell adhesion / nectin / afadin / cadherin / epithelial cells / adherens Junctions / commissural axons / floor plate / ドミナント・ネガティブ変異体 / タイト・ジャンクション

Research Abstract

We have found a novel cell-cell adhesion system consisting of nectin, an immunoglobulin-like adhesion molecule, and afadin, an F-actin-binding protein. This nectin-afadin system organizes adherens and tight junctions in epithelial cells. During the support from 2003 to 2004, we have studied the functions and mode of action of the nectin-afadin system. The results obtained are as follows :
1.A fragment of N-cadherin lacking its extracellular region serves as a dominant negative mutant(DN) and inhibits cell-cell adhesion activity of E-cadherin, but its mode of action remains to be elucidated. We have suggested that N-cadherin DN competitively inhibits the association of the endogenous nectin-afadin system with the endogenous E-cadherin-catenin system and thereby reduces the cell-cell adhesion activity of E-cadherin.
2.Nectin is necessary and sufficient for the recruitment of E-cadherin to the nectin-based cell-cell adhesion sites and involved in the formation of E-cadherin-based adherens junctions.
3.The nectin-afadin system is involved in dynamic epithelial remodeling during mouse development.
4.The contacts between the commissural axons and the floor plate cells are mediated by the hetero-trans-interaction between nectin-1 and nectin-3 and involved in regulation of the trajectory of the commissural axons.

Research Products

• [Journal Article] Expression patterns of nectins and afadin during epithelial remodeling in the mouse embryo. (2004)
  • Author(s): Okabe, N.
  • Journal Title: Dev.Dyn. 230 Pages: 174-186
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contacts between the commissural axons and the floor plate cells are mediated by nectins. (2004)
  • Author(s): Okabe, N.
  • Journal Title: Dev.Biol. 273 Pages: 244-256
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Roles of nectins in cell adhesion, migration, and polization. (2004)
  • Author(s): Nakanishi, H
  • Journal Title: Biol.Chem. 385 Pages: 885-892
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression patterns of nectins and afadin uring epithelial remodeling in the mouse embryo. (2004)
  • Author(s): Okabe, N., Ozaki-Kuroda, K., Nakanishi, H., Shimizu, K., Takai, Y.
  • Journal Title: Dev.Dyn. 230 Pages: 174-186
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contacts between the commissural axons and the floor plate cells are mediated by nectins. (2004)
  • Author(s): Okabe, N., Shimizu, K., Ozaki-Kuroda, K., Nakanishi, H., Morimoto, K., Takeuchi, M., Katsumaru, H., Murakami, F., Takai, Y.
  • Journal Title: Dev.Biol. 273 Pages: 244-256
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Roles of nectins in cell adhesion, migration, and polization. (2004)
  • Author(s): Nakanishi, H., Takai, Y.
  • Journal Title: Biol.Chem. 385 Pages: 885-892
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Roles of nectins in cell adhesion, migration, and polization. (2004)
  • Author(s): Nakanishi, H.
  • Journal Title: Biol.Chem. 385 Pages: 885-892
• [Journal Article] Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion. (2003)
  • Author(s): Honda, T.
  • Journal Title: Genes Cells 8 Pages: 51-63
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of nectin in formation of E-cadherin-based adherens junctions in keratinocytes---Analysis with the N-cadherin dominant negative mutant. (2003)
  • Author(s): Tanaka, Y.
  • Journal Title: Mol.Biol.Cell 14 Pages: 1597-1609
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The expression of nectin-1α in normal human skin and various skin tumors. (2003)
  • Author(s): Matsushima, H.
  • Journal Title: Eur.J.Dermatol. 148 Pages: 755-762
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel rabconnectin-binding protein that directly binds a GDP/GTP exchange protein for the Rab3A small G protein implicated in Ca^<2+>-dependent exocytosis of neurotransmitter. (2003)
  • Author(s): Kawabe, H.
  • Journal Title: Genes Cells 8 Pages: 537-546
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion. (2003)
  • Author(s): Honda, T., Shimizu, K., Kawakatsu, T., Yasumi, M., Shingai, T., Fukuhara, A., Inagaki, M., Ozaki-Kuroda, K., Irie, K., Nakanishi, H., Takai, Y.
  • Journal Title: Genes Cells 8 Pages: 51-63
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of nectin in formation of E-cadherin-based adherens junctions in keratinocytes---Analysis with the N-cadherin dominant negative mutant. (2003)
  • Author(s): Tanaka, Y., Nakanishi, H., Kakunaga, S., Okabe, N., Kawakatsu, T., Shimizu, K., Takai, Y.
  • Journal Title: Mol.Biol.Cell 14 Pages: 1597-1609
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The expression of nectin-1a in normal human skin and various skin tumors. (2003)
  • Author(s): Matsushima, H., Utani, A., Endo, H., Matsuura, H., Kakuta, M., Nakamura, Y., Matsuyoshi, N., Matsui, C., Nakanishi, H., Takai, Y., Shinkai, H.
  • Journal Title: Eur.J.Dermatol. 148 Pages: 755-762
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel rabconnectin-binding protein that directly binds a GDP/GTP exchange protein for the Rab3A small G protein implicated in Ca^<2+>-dependent exocytosis of neurotransmitter. (2003)
  • Author(s): Kawabe, H., Sakisaka, T., Yasumi, M., Shingai, T., Izumi, G., Nagano, F., Deguchi-Tawarada, M., Takeuchi, M., Nakanishi, H., Takai, Y.
  • Journal Title: Genes Cells 8 Pages: 537-546
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Honda, T.: "Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion."Genes Cells. 8. 51-63 (2003)
• [Publications] Tanaka, Y.: "Role of pectin in formation of E-cadherin-based adherens junctions in keratinocytes---Analysis with the N-cadherin dominant negative mutant."Mol.Biol.Cell. 14. 1597-1609 (2003)
• [Publications] Matsushima, H.: "The expression of nectin-1α in normal human skin and various skin tumors."Eur.J.Dermatol.. 148. 755-762 (2003)
• [Publications] Kawabe, H.: "A novel rabconnectin-binding protein that directly binds a GDP/GTP exchange protein for the Rab3A small G protein implicated in ca^<2+>-dependent exocytosis of neurotransmitter."Genes Cells. 8. 537-546 (2003)
• [Publications] Okabe, N.: "Expression patterns of nectins and afadin during epithelial remodeling in the mouse embryo."Developmental Dynamics. (in press).
• [Publications] Yamada, Y.: "Differential activation of the luteinizing hormone β-subunit promoter by activin and gonadotropin-releasing hormone. A role for the mitogen-activated protein kinase signaling pathway in LβT2 gonadotrophs."Biol.Reprod.. 70. 236-243 (2004)