A control structure of a nervous system synapse morphosis by a cell adhesion molecule.

• Project/Area Number: 16590142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Mie University
• Principal Investigator: MIZOGUCHI Akira Mie University, Department of Anatomy, School of Medicine, Professor, 大学院・医学系研究科, 教授 (90181916)
• Co-Investigator(Kenkyū-buntansha): KIMURA Kazushi Mie University, Department of Anatomy, School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (20314180) ; 栢原 哲郎 三重大学, 医学部, 講師 (20024705)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Cell adhesion / Synapse formation / Nectin / Immuno globulin / Margarita Island syndrome / Mental retardation / Memory formation / Hippocampus / 精神発達遅延 / シナプス / マイクロアレイ

Research Abstract

Nectins are Ca^<2+>-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, nectin-1 and nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interaction plays a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a nectin- and actin filament-binding protein. Inhibition of nectin-1-and nectin-3-based adhesion by in nectin-1 -/- mice resulted in the abnormal formation of synapses (Honda et al., 2006). Taken together, it is likely that nectins are involved in the formation of synapses in cooperation with N-cadherin. This role of nectins is consistent with the finding that mutations in the nectin-1 gene are responsible for cleft lip/palate-ectodermal dysplasia, which is characterized by mental retardation in addition to ectodermal dysplasia.
For identification of a novel molecule that have cell-aggregation activity and is involved in synapse formation, we made a subtraction library for developmental hippocampus (P10-P5). This library was transfected into fibroblasts and the transfected cells were performed with cell-aggregation assay. We identified a voltage-gated K^+ channel as a cell adhesion molecule (Kimura et al., in preparation for submission). Furthermore, we also found that aquaproin 4, a water channel, has cell aggregation activity (Hiroaki et al. 2006).

Research Products

• [Journal Article] Choroid plexus ependymal cells host neural progenitor cells in the rat. (2006)
  • Author(s): Itokazu Y, Kitada M, Dezawa M, Mizoguchi A, Matsumoto N, Shimazu A, Ide C.
  • Journal Title: Glia. 53・1 Pages: 32-42
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of nectins in the formation of puncta adherentia junctions and the mossy fiber trajectory in the mouse hippocampus. (2006)
  • Author(s): IHonda T, Sakisaka T, Yamada T, Kumazawa N, Hoshino T, Kajita M, Kayahara T, Ishizaki H, Tanaka-Okamoto M, Mizoguchi A, Manabe T, Miyoshi J, Takai Y.
  • Journal Title: Mol Cell Neurosci. 31・2 Pages: 315-325
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Implications of the Aquaporin-4 Structure on Array Formation and Cell Adhesion. (2006)
  • Author(s): Hiroaki Y, Tani K, Kamegawa A, Gyobu N, Nishikawa K, Suzuki H, Walz T, Sasaki S, Mitsuoka K, Kimura K, MIzoguchi A, Fujiyoshi Y.
  • Journal Title: J Mol Biol. 355・4 Pages: 628-639
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Differential localization and regulation of stargazin-like protein, gemma-8 and stargazin in the plasma membrane of hippocampal and cortical neurons. (2006)
  • Author(s): Inamura M, Itakura M, Okamuto H, Hoka S, Mizoguchi A, Fukazawa Y, Shigemoto R, Yamamori S, Takahashi M.
  • Journal Title: Neurosci Res. 55-1 Pages: 45-53
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterizationg and function of MYPT2, a target subunit of myosin phosphatase in heart. (2006)
  • Author(s): Okamoto R, Kato T, Mizoguchi A, Takahashi N, Nakakuki T, Mizutani H, Isaka N, Imanaka-Yoshida K, Kaibuchi K, Lu Z, Mabuchi K, Tao T, Hartshorne DJ, Nakano T, Ito M.
  • Journal Title: Cell Signal. (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Choroid plexus ependymal cells host neural progenitor cells in the rat. (2006)
  • Author(s): Itokazu Y, Kitada M, Dezawa M, Mizoguchi A, Matsumoto N, Shimizu A, Ide C.
  • Journal Title: Glia. 53-1 Pages: 32-42
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of nectins in the formation of puncta adherentia junctions and the mossy fiber trajectory in the mouse hippocampus. (2006)
  • Author(s): Honda T, Sakisaka T, Yamada T, Kumazawa N, Hoshino T, Kajita M, Kayahara T, Ishizaki H, Tanaka-Okamoto M, Mizoguchi A, Manabe T, Miyoshi J, Takai Y.
  • Journal Title: Mol Cell Neurosci. 31-2 Pages: 315-325
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Implications of the Aquaporin-4 Structure on Array Formation and Cell Adhesion. (2006)
  • Author(s): Hiroaki Y, Tani K, Kamegawa A, Gyobu N, Nishikawa K, Suzuki H, Walz T, Sasaki S, Mitsuoka K, Kimura K, Mizoguchi A, Fujiyoshi Y.
  • Journal Title: J Mol Biol. 355-4 Pages: 628-639
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart. (2006)
  • Author(s): Okamoto R, Kato T, Mizoguchi A, Takahashi N, Nakakuki T, Mizutani H, Isaka N, Imanaka-Yoshida K, Kaibuchi K, Lu Z, Mabuchi K, Tao T, Hartshorne DJ, Nakano T, Ito M.
  • Journal Title: Cell Signal. In press
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Differential localization and regulation of stargazin-like protein, gamma-8 and stargazin in the plasma membrane of hippocampal and cortical neurons. (2006)
  • Author(s): Inamura M, Itakura M, Okamoto H, Hoka S, Mizoguchi A, Fukazawa Y, Shigemoto R, Yamamori S, Takahashi M.
  • Journal Title: Neurosci Res. 55-1 Pages: 45-53
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Choroid plexus ependymal cells host neural progenitor cells in the rat. (2006)
  • Author(s): Itokazu Y, Kitada M, Dezawa M, Mizoguchi A, Matsumoto N, Shimizu A, Ide C.
  • Journal Title: Glia. 53・1 Pages: 32-42
• [Journal Article] Implications of the Aquaporin-4 Structure on Array Formation and Cell Adhesion. (2006)
  • Author(s): Hiroaki Y, Tani K, Kamegawa A, Gyobu N, Nishikawa K, Suzuki H, Walz T, Sasaki S, Mitsuoka K, Kimura K, Mizoguchi A, Fujiyoshi Y.
  • Journal Title: J Mol Biol. 355・4 Pages: 628-639
• [Journal Article] Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart. (2006)
  • Author(s): Okamoto R, Kato T, Mizoguchi A, Takahashi N, Nakakuki T, Mizutani H, Isaka N, Imanaka-Yoshida K, Kaibuchi K, Lu Z, Mabuchi K, Tao T, Hartshorne DJ, Nakano T, Ito M.
  • Journal Title: Cell Signal. (In press)
• [Journal Article] Differential localization and regulation of stargazin-like protein, gamma-8 and stargazin in the plasma membrane of hippoca mpal and cortical neurons. (2006)
  • Author(s): Inamura M, Itakura M, Okamoto H, Hoka S, Mizoguchi A, Fukazawa Y, Shigemoto R, Yamamori S, Takahashi M.
  • Journal Title: Neurosci Res. (In press)
• [Journal Article] Nectin-like molecule-1/TSLL1/SynCAM3 : a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes. (2005)
  • Author(s): Kakunage S, Ikeda W, Itoh S, Deguchi-Tawarada M, Ohtsuka T, Mizoguchi A, Takai Y.
  • Journal Title: J Cell Sci. 118/Pt6 Pages: 1267-1277
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma. (2005)
  • Author(s): Toiyama Y, Mizoguchi A, Kimura K, Araki T, Yoshiyama S, Sakaguchi K, Miki C, Kusunoki M
  • Journal Title: World J Gastroenterol 11・33 Pages: 5151-5155
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nectin-like molecule-1/TSLL1/SynCAM3 : a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes. (2005)
  • Author(s): Kakunaga S, Ikeda W, Itoh S, Deguchi-Tawarada M, Ohtsuka T, Mizoguchi A, Takai Y.
  • Journal Title: J Cell Sci. 118-Pt6 Pages: 1267-1277
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma. (2005)
  • Author(s): Toiyama Y, Mizoguchi A, Kimura K, Araki T, Yoshiyama S, Sakaguchi K, Miki C, Kusunoki M
  • Journal Title: World J Gastroenterol. 11-33 Pages: 5151-5155
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nectin-like molecule-1/TSLL1/SynCAM3 : a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-functional contact sites of presynaptic nerve terminals, axons and glia cell processes. (2005)
  • Author(s): Kakunaga S, Ikeda W, Itoh S, Deguchi-Tawarada M, Ohtsuka T, Mizoguchi A, Takai Y.
  • Journal Title: J Cell Sci. 118・Pt6 Pages: 1267-1277
• [Journal Article] Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma. (2005)
  • Author(s): Toiyama Y, Mizoguchi A, Kimura K, Araki T, Yoshiyama S, Sakaguchi K, Miki C, Kusunoki M
  • Journal Title: World J Gastroenterol. 11・33 Pages: 5151-5155
• [Journal Article] Nectin-like molecule-1/TSLL1/SynCAM3 : A neural tissue-specific immunoglob ulin-like cell-cell adhesion molecule localizing at non junctional contact sites where presynaptic nerve terminals, axons, and glia cell processes contact (2005)
  • Author(s): Kakunaga S, et al.
  • Journal Title: J Cell Scie. In press
• [Journal Article] Neurite outgrowth from hippocampal neurons is promoted by choroid plexus ependymal cells in vitro. (2004)
  • Author(s): Kimura K, et al.
  • Journal Title: J Neurocytol. 33・4 Pages: 465-476
• [Journal Article] A novel mode of action of an ArfGAP, AMAP2/PAG3/ Papalpha, in Arf6 function. (2004)
  • Author(s): Hashimoto S, et al.
  • Journal Title: J Biol Chem. 279・3 Pages: 37677-37684
• [Journal Article] The secretory granule-associated protein CAPS2 regulates neurotrophin release and cell survival. (2004)
  • Author(s): Sadakata T, et al.
  • Journal Title: J Neurosci. 24・1 Pages: 43-52
• [Journal Article] Nectin-Afadin細胞接着機構 (2004)
  • Author(s): 溝口 明
  • Journal Title: 生体の科学 55・5 Pages: 438-439