Roles of afadin and nectins in synapse formation

• Project/Area Number: 24590354
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: MANDAI Kenji 神戸大学, 医学(系)研究科(研究院), 准教授 (50322186)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: シナプス形成 / アファディン / ネクチン / 海馬 / 大脳新皮質 / 中脳水道 / 嗅球 / 分子神経生物学 / シナプス

Outline of Final Research Achievements

We investigated the roles of afadin in synapse formation and synaptic functions in the hippocampus. At mossy fiber-CA3 pyramidal cell synapses, afadin was required for the accumulation of the PAJ components, nectin-1, nectin-3 and N-cadherin, and for the accumulation of the presynaptic components, VGLUT1 and bassoon. In addition, afadin regulated pre- and post-synaptic functions in cultured hippocampal excitatory neurons. We also investigated the roles of afadin in the developing brain. In the midbrain, afadin was required for morphogenesis of the cerebral aqueduct, and in the neocortex, afadin was required for the formation of the six-layered laminated architecture by regulating neural migration. Furthermore, we investigated the roles of nectin-1 in the olfactory bulb and showed that nectin-1 constituted a novel adhesion apparatus that tethered mitral cell dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb.

Research Products

• [Journal Article] Nectins and nectin-like molecules in development and disease. (2015)
  • Author(s): Mandai K, Rikitake Y, Mori M, Takai Y.
  • Journal Title: Curr Top Dev Biol. Volume: 112 Pages: 197-231
  • DOI: 10.1016/bs.ctdb.2014.11.019
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nectin-1 spots as a novel adhesion apparatus that tethers mitral cell lateral dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb. (2015)
  • Author(s): Inoue, T., Fujiwara, T., Rikitake, Y., Maruo, T., Mandai, K., Kimura, K., Kayahara, T., Wang, S., Ioth, Y., Sai, K., Mori, M., Mori, K., Mizoguchi, A., & Takai, Y.
  • Journal Title: J Comp Neurol.
  • Peer Reviewed
• [Journal Article] Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin. (2015)
  • Author(s): Yamamoto, H., Mandai, K., Konno, D., Maruo, T., Matsuzaki, F., & Takai, Y.
  • Journal Title: Brain Res.
  • Peer Reviewed
• [Journal Article] Roles of nectins and nectin-like molecules in the nervous system. (2014)
  • Author(s): Mori, M., Rikitake, Y., Mandai, K., & Takai, Y.
  • Journal Title: Adv Neurobiol. Volume: 8 Pages: 91-116
• [Journal Article] s-Afadin binds more preferentially to the cell adhesion molecules nectins than l-afadin. (2014)
  • Author(s): Kobayashi R, Kurita S, Miyata M, Maruo T, Mandai K, Rikitake Y, Takai Y.
  • Journal Title: Genes Cells. Volume: 19 Issue: 12 Pages: 853-863
  • DOI: 10.1111/gtc.12185
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Afadin regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons. (2014)
  • Author(s): Toyoshima D, Mandai K, Maruo T, Supriyanto I, Togashi H, Inoue T, Mori M, Takai Y.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: e89763-e89763
  • DOI: 10.1371/journal.pone.0089763
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Afadin/AF-6 and Canoe: Roles in cell adhesion and beyond (2013)
  • Author(s): Kenji Mandai
  • Journal Title: Progress in Molecular Biology and Translational Science Volume: 116 Pages: 433-454
  • DOI: 10.1016/b978-0-12-394311-8.00019-4
  • Peer Reviewed
• [Journal Article] The role of nectins in different types of cell-cell adhesion. (2012)
  • Author(s): Rikitake, Y.
  • Journal Title: J Cell Sci. Volume: 125 Issue: 16 Pages: 3713-3722
  • DOI: 10.1242/jcs.099572
  • Peer Reviewed
• [Journal Article] Immunoglobulin superfamily receptors and adherens junctions. (2012)
  • Author(s): Shimono, Y.
  • Journal Title: Subcell Biochem. Volume: 60 Pages: 137-170
  • DOI: 10.1007/978-94-007-4186-7_7
  • ISBN: 9789400741850, 9789400741867
  • Peer Reviewed
• [Presentation] SBF-SEM 3D reconstitution analysis reveals alterations in composition and morphology of mouse hippocampal mossy fiber synapses by afadin knockout. (2015)
  • Author(s): Fujiwara, T., Wang, S., Itoh, Y., Sai, K., Kaito, A., Miyazaki, N., Murata, K., Maruo, T., Yamamoto, H., Mandai, K., Takai, Y., & Mizoguchi, A.
  • Organizer: 第120回日本解剖学会全国学術集会・第92回日本生理学会大会合同大会
  • Place of Presentation: 神戸国際会議場・展示場（兵庫県神戸市）
  • Year and Date: 2015-03-21
• [Presentation] Afadin plays an important role in formation of puncta adherentia junction and differentiation of presynapses in hippocampal neurons. (2014)
  • Author(s): Toyoshima, D., Mandai, K., Maruo, T., Supriyanto, I., Togashi, H., Inoue, T., Mori, M., & Takai, Y.
  • Organizer: Society for Neuroscience, 2014 Annual Meeting
  • Place of Presentation: Washington DC, U.S.A.
  • Year and Date: 2014-11-19
• [Presentation] Pathophysiological roles of afadin in the brain development. (2014)
  • Author(s): Yamamoto, H., Mandai, K., Maruo, T., Konno, D., & Matsuzaki, F.
  • Organizer: 第37回日本神経科学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-12
• [Presentation] Abnormal radial glial scaffold for migrating neurons leads to formation of the double cortex in afadin-deficient mice. (2014)
  • Author(s): Yamamoto, H., Mandai, K., Konno, D., Maruo, T., Matsuzaki, F., & Takai, Y.
  • Organizer: Cold Spring Harbor Laboratory Meeting, Glia in Health & Disease
  • Place of Presentation: Cold Spring Harbor, NY, U.S.A.
  • Year and Date: 2014-07-20
• [Presentation] Afadin is involved in synaptogenesis of hippocampal neurons.
  • Author(s): Maruo, T., Toyoshima, D., Mandai, K., Togashi, H., Inoue, T., Yamamoto, H., Miyoshi, J., Supriyanto, I., Mori, M., and Takai, Y.
  • Organizer: 第36回日本神経科学会大会
  • Place of Presentation: 京都