Search for novel trafficking pathway dependent on microtubule plus-end-tracking proteins (+TIPs)

• Project/Area Number: 25650071
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KIYOSUE Yuko 独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, ユニットリーダー (90568403)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 細胞骨格 / 微小管 / 細胞極性 / 物質輸送 / 細胞分裂 / 高解像イメージング / 細胞内輸送 / 微小管プラス端集積因子 / 分泌

Outline of Final Research Achievements

This research project aimed at search for novel trafficking pathway dependent on microtubule plus-end-tracking proteins (+TIPs), which connect microtubule ends with subcellular structures, on the supposition that these molecules serve as platforms for loading/unloading or sorting of cargos transported by motor proteins. Our analyses focused on LL5 protein and APC tumor suppressor protein led to the discovery of novel regulatory mechanisms for trafficking and mouse phenotypes. We also found a crosstalk between APC tumor suppressor and an important mitotic kinase involved in the transport of chromosomes. In addition, we succeeded in the 3D tracking of microtubule growth throughout the cell cytoplasm using the recently developed lattice light-sheet microscope, which enables 3D scanning at subsecond intervals with high spatial resolution.

Research Products

• [Journal Article] 3D革命 ― 生命活動の真の姿を照らし出す次世代蛍光顕微鏡技術 (2015)
  • Author(s): 下澤東吾, 清末優子
  • Journal Title: 実験医学 Volume: 33 Pages: 458-461
• [Journal Article] 2014年ノーベル化学賞：超解像顕微鏡の開発 (2014)
  • Author(s): 藤田克昌, 岡田康志, 清末優子
  • Journal Title: 実験医学 Volume: 32 Pages: 3071-3076
• [Journal Article] Lattice Light Sheet Microscopy: Imaging Molecules, Cells, and Embryos at High Spatiotemporal Resolution (2014)
  • Author(s): Chen BC, Legant WR, Wang K, Shao L, Milkie DE, Davidson MW, Janetopoulos C, Wu XS, Hammer JA 3rd, Liu Z, English BP, Mimori-Kiyosue Y, Romero DP, Ritter AT, Lippincott-Schwartz J, Fritz-Laylin L, Mullins RD, Mitchell DM, Bembenek JN, Reymann AC, Bohme R, Grill SW, Wang JT, Seydoux G, Tulu US, Kiehart DP, Betzig E.
  • Journal Title: Science Volume: 346 Issue: 6208 Pages: 1257998-1257998
  • DOI: 10.1126/science.1257998
  • Peer Reviewed
• [Journal Article] 生体試料深部の高速・高精細な 蛍光イメージング装置の開発と応用 (2014)
  • Author(s): 下澤東吾, 清末優子
  • Journal Title: バイオインダストリー Volume: 7月号 Pages: 43-50
• [Journal Article] CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor. (2013)
  • Author(s): van der Vaart B, van Riel WE, Doodhi H, Kevenaar JT, Katrukha EA, Gumy L, Bouchet BP, Grigoriev I, Spangler SA, Yu KL, Wulf PS, Wu J, Lansbergen G, van Battum EY, Pasterkamp RJ, Mimori-Kiyosue Y, Demmers J, Olieric N, Maly IV, Hoogenraad CC, Akhmanova A.
  • Journal Title: Dev Cell. Volume: 27 Issue: 2 Pages: 145-160
  • DOI: 10.1016/j.devcel.2013.09.010
  • Peer Reviewed
• [Journal Article] スピニングディスク共焦点顕微鏡の改良と組織・個体内部の観察への応用 (2013)
  • Author(s): 下澤東吾, 清末優子.
  • Journal Title: 生体の科学 Volume: 64 Pages: 564-570
• [Presentation] Toward high-speed high-resolution 3D imaging (2015)
  • Author(s): 清末優子
  • Organizer: 第120回日本解剖学会 / 第92回日本生理学会 合同大会
  • Place of Presentation: 神戸コンベンションセンター（神戸）
  • Year and Date: 2015-03-23
  • Invited
• [Presentation] PHLDB1/LL5αのPHドメインの部分欠損はマウスの水晶体脱臼白内障を引き起こす (2014)
  • Author(s): 渡部 桂, 和田 健太, 松島 芳文, 設楽 浩志, 清末 優子, 吉川 欣亮
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-11-27
• [Presentation] 高速高精細3Dイメージングへのチャレンジ (2014)
  • Author(s): 下澤東吾, 清末優子
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良県新公会堂（奈良）
  • Year and Date: 2014-06-13
  • Invited
• [Presentation] Challenges toward High-Speed, High-Resolution 3D Imaging (2014)
  • Author(s): 下澤東吾, 清末優子
  • Organizer: 日本顕微鏡学会第70回記念学術講演会
  • Place of Presentation: 幕張メッセ 国際会議場（千葉）
  • Year and Date: 2014-05-13
  • Invited
• [Remarks] 所属研究機関ラボHP
  • URL: http://www.clst.riken.jp/ja/science/labs/bdi/biosys/cda/
• [Remarks] 格子光シート顕微鏡が明かす細胞分裂の仕組み－生命活動の真の姿を照らし出す新たな蛍光顕微鏡－
  • URL: http://www.riken.jp/pr/topics/2014/20141029_1/
• [Remarks] 研究室ホームページ
  • URL: http://www.cdb.riken.jp/oia/
• [Remarks] [報道発表資料] 生物内部を高速・高精細にイメージングが可能に
  • URL: http://www.riken.jp/pr/press/2013/20130212_1/