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Cell adhesion machine-associated signaling mechanisms regulating cell behavior

Research Project

Project/Area Number 15002014
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionRIKEN

Principal Investigator

TAKEICHI Masatoshi  RIKEN, Center for Developmental Biology, Group Director, 高次構造形成研究グループ, グループディレクター (00025454)

Co-Investigator(Kenkyū-buntansha) MAEKAWA Midori  RIKEN, Center for Developmental Biology, Research Scientist, 高次構造形成研究グループ, 専門職研究員 (70314185)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥332,800,000 (Direct Cost: ¥256,000,000、Indirect Cost: ¥76,800,000)
Fiscal Year 2006: ¥81,900,000 (Direct Cost: ¥63,000,000、Indirect Cost: ¥18,900,000)
Fiscal Year 2005: ¥81,900,000 (Direct Cost: ¥63,000,000、Indirect Cost: ¥18,900,000)
Fiscal Year 2004: ¥81,900,000 (Direct Cost: ¥63,000,000、Indirect Cost: ¥18,900,000)
Fiscal Year 2003: ¥87,100,000 (Direct Cost: ¥67,000,000、Indirect Cost: ¥20,100,000)
Keywordscadherin / catenin / cell adhesion / synapse / actin / Rho GEF / NMDA receptor / neuron / Cdc42 / Tuba / NAWSP / NMDAレセプター / 微小管 / Rho / 細胞運動 / 細胞骨格 / カルシウムポンプ
Research Abstract

1) αN-catenin is a cadherin-associated protein. We found that this protein is essential for the stability of synaptic contacts in hippocampal neurons.
2) Fat1 is a member of the cadherin superfamily. We showed that this large non-classic cadherin is localized at the basal portions of cell-cell contact, and regulates actin polymerization via its binding to Ena/VASP proteins.
3) We identified the role of the Cdc42-specific Rho GEF "Tuba". This enzyme regulates tension of cell-cell junctions, acting upstream of the Cdc42-N-WASP signaling pathway.
4) We discovered an unexpected movement of cadherin molecules at cell junctions, which was designated as "cadherin flow". This flow is mediated by retrograde actin flow, which also occurs at cell-cell contact sites.
5) We disclosed a novel signaling pathway for gene transcription in hippocampal neurons. Activation of the NMDA receptor resulted in N-terminal truncations of β-catenin, and the cleaved β-catenin was translocated into nuclei This process subsequently activated expression of the Fral gene. We also showed that this gene activation system also occurs in vivo.

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (59 results)

All 2007 2006 2005 2004 Other

All Journal Article (55 results) Publications (4 results)

  • [Journal Article] Basal-to-apical cadherin flow at cell junctions.2007

    • Author(s)
      Kametani, S.
    • Journal Title

      Nature Cell Biol. 9

      Pages: 92-98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] N-cadherin mediates cortical organization in the mouse brain2007

    • Author(s)
      Kadowaki, M.
    • Journal Title

      Develop. Biol. 304

      Pages: 22-33

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cornichon-like Protein (CNIL) Facilitates Secretion of HB-EGF and Regulates Proper Development of Cranial Nerves.2007

    • Author(s)
      Hoshino, H.
    • Journal Title

      Mol. Biol. Cell. 18

      Pages: 1143-1152

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NMDA Receptor activation induces calpain-mediated β-catenin cleavages for triggering gene expression.2007

    • Author(s)
      Abe, K.
    • Journal Title

      Neuron 53

      Pages: 387-397

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Cadherin-11 in synovial lining formation and pathology in arthritis.2007

    • Author(s)
      Lee, D.M.
    • Journal Title

      Science 315

      Pages: 1006-1010

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] p120-catenin regulates microtubule dynamics and cell migration in a cadherin-independent manner.2007

    • Author(s)
      Ichii, T.
    • Journal Title

      Genes to Cells (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Basal-to-apical cadherin flow at cell junctions.2007

    • Author(s)
      Kametani, Y., Takeichi, M
    • Journal Title

      Nature Cell BioL 9

      Pages: 92-98

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] N-cadherin mediates cortical organization in the mouse brain.2007

    • Author(s)
      Kadowaki, M., Nakamura, S., Machon, O., Krauss, S., Radice, G.L., Takeichi M
    • Journal Title

      Develop. Biol 304

      Pages: 22-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comichon-like Protein (CNIL) Facilitates Seaetion of HB-EGF and Regulates Proper Development of Cranial Naves.2007

    • Author(s)
      Hoshino, H, Uchida, T., Otsuki T., Kawamoto, S., Okubo, K, Takeichi, M., Chisaka, O.
    • Journal Title

      Mol Biol. Cell. 18

      Pages: 1143-1152

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NMDA Receptor activation induces calpain-mediated β-catenin cleavages for triggering gene expression.2007

    • Author(s)
      Abe, K, Takeichi, M
    • Journal Title

      Neuron 53

      Pages: 387-397

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cadherin-11 in synovial lining formation and pathology in arthritis.2007

    • Author(s)
      Lee, D.M, Kiener, H.P., Agarwal, S.K, Noss, E.H., Watts, G.F., Chisaka, O, Takeichi, M, Brenner, M.B.
    • Journal Title

      Science 315

      Pages: 1006-1010

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Basal-to-apical cadherin flow at cell junctions.2007

    • Author(s)
      Kametani, Y
    • Journal Title

      Nature Cell Biol. 9

      Pages: 92-98

    • Related Report
      2006 Annual Research Report
  • [Journal Article] N-cadherin mediates cortical organization in the mouse brain. Develop. Biol.2007

    • Author(s)
      Kadowaki, M.
    • Journal Title

      Develop. Biol. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cornichon-like Protein (CNIL) Facilitates Secretion of HB-EGF and Regulates Proper Development of Cranial Nerves.2007

    • Author(s)
      Hoshino, H.
    • Journal Title

      Mol Biol Cell (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cadherin-11 in synovial lining formation and pathology in arthritis.2007

    • Author(s)
      Lee, D.M.
    • Journal Title

      Science (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interneurite affinity is regulated by heterophilic nectin interactions in concert with the cadherin machinery.2006

    • Author(s)
      Togashi, H.
    • Journal Title

      J. Cell Biol. 174

      Pages: 141-151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] αN-catenin deficiency causes defects in axon migration and nuclear organization in restricted regions of the mouse brain.2006

    • Author(s)
      Uemura, M.
    • Journal Title

      Dev. Dynamics 235

      Pages: 2559-2566

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells. J. Cell Biol.2006

    • Author(s)
      Nakao, S.
    • Journal Title

      J. Cell Biol. 175

      Pages: 135-146

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells.2006

    • Author(s)
      Tanabe, K.
    • Journal Title

      Development 133

      Pages: 4085-4095

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] The cadherin superfamily in neuronal recognitions and interactions.2006

    • Author(s)
      Takeichi, M.
    • Journal Title

      Nature Reviews Neurosciences 8

      Pages: 11-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Temporal and spatial expression profiles of the Fat3 protein, a giant cadherin molecule, during mouse development.2006

    • Author(s)
      Nagae, S
    • Journal Title

      Develop. Dynamics 236

      Pages: 534-543

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interneurite affinity is regulated by heterophilic nectin interactions in concert with the cadherin machinery.2006

    • Author(s)
      Togashi, H, Miyoshi, J., Honda, T., Sakisaka, T., Takai, T., Takeichi, M.
    • Journal Title

      J. Cell Biol. 174

      Pages: 141-151

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] N-catenin deficiency causes defects in axon migration and nuclear organization in restricted regions of the mouse brain.2006

    • Author(s)
      Uemura, M., Takeichi, M
    • Journal Title

      Dev. Dynamics 235

      Pages: 2559-2566

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.2006

    • Author(s)
      Otani, T., Ichii, T., Aono, S., Takeichi, M
    • Journal Title

      J. Cell Biol. 175

      Pages: 135-146

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells.2006

    • Author(s)
      Tanabe, K, Takahashi, Y., Sato, Y., Kawakami, K, Takeichi, M., Nakagawa, S.
    • Journal Title

      Development 133

      Pages: 4085-4096

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The cadherin superfamily in neuronal recognitions and interactions.2006

    • Author(s)
      Takeichi, M
    • Journal Title

      Nature Reviews Neurosciences 8

      Pages: 11-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tamporal and spatial expression profiles of the Fat3 protein, a giant cadherin molecule, during mouse development.2006

    • Author(s)
      Nagae, S., Tanoue, T., Takeichi, M.
    • Journal Title

      Develop. Dynamics 236

      Pages: 534-543

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interneurite affinity is regulated by heterophilis nectin interactions in concert with the cadherin machinery.2006

    • Author(s)
      Togashi, H.
    • Journal Title

      J. Cell Biol. 174

      Pages: 141-151

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.2006

    • Author(s)
      Otani, T.
    • Journal Title

      J. Cell Biol. 175

      Pages: 135-146

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Temporal and spatial expression profiles of the Fat3 protein, a giant cadherin molecule, during mouse development.2006

    • Author(s)
      Nagae, S.
    • Journal Title

      Develop. Dynamics 236

      Pages: 534-543

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distribution of OL-protocadherin in axon fibers in the developing chick nervous system.2005

    • Author(s)
      Nakao, S.
    • Journal Title

      Brain Res. Mol. Brain Res. 7

      Pages: 294-308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synaptic contact dynamics controlled by cadherin and cate nins.2005

    • Author(s)
      Takeichi, M.
    • Journal Title

      Trends in Cell Biol. 15

      Pages: 216-221

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] New insights into Fat cadherins.2005

    • Author(s)
      Tanoue, T.
    • Journal Title

      J. Cell Sci. 118

      Pages: 2347-2353

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Wnt2b inhibits differentiation of retinal progenitor cells in the absence of Notch activity by downregulating the expression of proneural genes.2005

    • Author(s)
      Kubo, F.
    • Journal Title

      Development 132

      Pages: 2759-2770

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Distribution of OL-protocadherin in axon fibers in the developing chick nervous system.2005

    • Author(s)
      Nakao, S., Uemura, M., Aoki, E., Suzuki, S.T., Takeichi, M, Hirano, S.
    • Journal Title

      Brain Res. Mol. Brain Res. 134

      Pages: 294-308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synaptic contact dynamics controlled by cadherin and catenins.2005

    • Author(s)
      Takeichi, M, Abe, K
    • Journal Title

      Trends in Cell Biol. 15

      Pages: 216-221

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] New insights into Fat cadherins.2005

    • Author(s)
      Tanoue, T., Takeichi, M
    • Journal Title

      J. Cell Sci. 118

      Pages: 2347-2353

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Wnt2b inhibits differentiation of retinal progenitor cells in the absence of Notch activity by downregulating the expression of proneural genes.2005

    • Author(s)
      Kubo, F., Takeichi, M., Nakagawa, S.
    • Journal Title

      Development 132

      Pages: 2759-2770

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Distribution of OL-protocadherin in axon fibers in the developing chick nervous system.2005

    • Author(s)
      Nakao, S., Uemura, M., Aoki, E., Suzuki, S.T., Takeichi, M., Hirano, S.
    • Journal Title

      Brain Res.Mol.Brain Res. 134

      Pages: 294-308

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Synaptic contact dynamics controlled by cadherin and catenins.2005

    • Author(s)
      Takeichi, M., Abe, K.
    • Journal Title

      Trends in Cell Biol. 15

      Pages: 216-221

    • Related Report
      2005 Annual Research Report
  • [Journal Article] New insights into Fat cadherins.2005

    • Author(s)
      Tanoue, T., Takeichi, M.
    • Journal Title

      J.Cell Sci. 118

      Pages: 2347-2353

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Distribution of OL-protocadherin in axon fibers in the developing chick nervous system.2005

    • Author(s)
      Nakao, S., Uemura, M., Aoki, E., Suzuki, S.T., Takeichi, M., Hirano, S.
    • Journal Title

      Brain Res.Mol.Brain Res. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Synaptic contact dynamics controlled by cadherin and catenins.2005

    • Author(s)
      Takeichi, M., Abe, K.
    • Journal Title

      Trends in Cell Biol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of a nonchordate-type classic cadherin in vertebrates : Chicken Hz cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate-specific domain complex.2004

    • Author(s)
      Tanabe, K.
    • Journal Title

      Dev. Dynamics 229

      Pages: 899-906

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stability of dendritic spines and synaptic contacts is controlled by αN-catenin.2004

    • Author(s)
      Abe, K.
    • Journal Title

      Nature Neuroscience 7

      Pages: 357-363

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.2004

    • Author(s)
      Tanoue, T.
    • Journal Title

      J. Cell Biol. 165

      Pages: 517-528

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin.2004

    • Author(s)
      Shima, Y.
    • Journal Title

      Develop. Cell 7

      Pages: 205-216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of a nonchordate -type classic cadherin in vertebrates : Chicken Hz cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate-specific domain complex.2004

    • Author(s)
      Tanabe, K, Takeichi, M, Nakagawa, S.
    • Journal Title

      Dev. Dynamics 229

      Pages: 899-906

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stability of dendritic spines and synaptic contacts is controlled by αN-catenin.2004

    • Author(s)
      Abe, K, Chisaka, O., van Roy, F., Takeichi, M.
    • Journal Title

      Nature Neuroscience 7

      Pages: 357-363

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mammalian Fatl cadherin regulates actin dynamics and cell-cell contact2004

    • Author(s)
      Tanoue, T., Takeichi, M
    • Journal Title

      J. Cell Biol. 165

      Pages: 517-528

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin.2004

    • Author(s)
      Shima, Y., Kengaku, M, Hirano, T., Takeichi, M., Uemura T.
    • Journal Title

      Develop. Cell 7

      Pages: 205-216

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stability of dendritic spines and synaptic contacts is controlled by αN-catenin.2004

    • Author(s)
      Abe, K., Chisaka, O., van Rov, F., Takeichi, M.
    • Journal Title

      Nature Neuroscience 7

      Pages: 357-363

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.2004

    • Author(s)
      Tanoue, T., Takeichi, M.
    • Journal Title

      J.Cell Biol. 165

      Pages: 517-528

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin.2004

    • Author(s)
      Shima, Y., Kengaku, M., Hirano, T., Takeichi, M., Uemura T.
    • Journal Title

      Develop.Cell 7

      Pages: 205-216

    • Related Report
      2004 Annual Research Report
  • [Journal Article] p120-catenin regulates microtubule dynamics and cell migration in a cadherin-independent manner

    • Author(s)
      Ichii, T., Takeichi, M
    • Journal Title

      Genes to Cells (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Publications] Kubo, F., Takeichi, M., Nakagawa, S: "Wnt2b controls retinal cell differentiation at the ciliary marginal zone."Development. 130. 587-598 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakagawa, S., Takada, S., Takada, R., Takeichi, M.: "Identification of the laminar-inducing factor : Wnt-signal from the anterior rim induces correct laminar formation of the neural retina in vitro."Develop.Biol.. 260. 414-425 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanabe, K., Takeichi, M., Nakagawa, S.: "Identification of a nonchordate-type classic cadherin in vertebrates : Chicken Hz cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate-secific domain complex."Dev.Dynamics. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abe, K., Chisaka, O., van Roy, F., Takeichi, M.: "Stability of dendritic spines and synaptic contacts is controlled by αN-catenin."Nature Neuroscience. (in press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2018-03-28  

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