The mechanism for determining the position of contraction ring formation in human erythroblast enucleation.

• Project/Area Number: 15K19540
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Akita University
• Principal Investigator: Ubukawa Kumi 秋田大学, 医学部, 助教 (70646554)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヒト赤芽球 / 脱核 / 細胞極性 / Cdc42 / mDia2 / ダイニン / EHNA(阻害剤） / 微小管形成中心(MTOC) / EHNA（阻害剤） / 微小管形成中心（MTOC）

Outline of Final Research Achievements

Mammalian erythroblasts undergo enucleation through a process thought to be similar to cytokinesis. However, the mechanism of position determination of contraction ring in enucleation is still unknown.
We investigated the presence of various molecules involved in cell division on the proliferation of human colony-forming unis-erythroid and erythroblasts. Cdc42, mDia2 and mDia3 were involved determining the position of contraction ring formation during erythroblast enucleation. Furthermore, Cdc42 inhibitor blocked proliferation of CFU-Es in a dose-dependent manner and reduced the enucleation ratio of erythroblasts. These results suggest that Cdc42 plays an important role in both cytokinesis and cell polarization through the regulation of dynein and actin filament organization during terminal differentiation of human erythroblasts.

Research Products

• [Journal Article] Erythroblast enucleation is a dynein-dependent process. (2016)
  • Author(s): Kobayashi I, Ubukawa K, Sugawara K, Asanuma K, Guo Y, Yamashita J, Takahashi N, Sawada K, Nunomura W.
  • Journal Title: Exp. Hematol. Volume: 44 Issue: 4 Pages: 247-256
  • DOI: 10.1016/j.exphem.2015.12.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Oxygen concentration-dependent regulation of erythropoiesis in human erythroblast. (2017)
  • Author(s): Goto T
  • Organizer: ASCB/EMBO 2017 Meeting
  • Int'l Joint Research
• [Presentation] Cdc42 regulates dynein and actin in terminal differentiation of human erythroblast. (2017)
  • Author(s): Goto T
  • Organizer: ASCB/EMBO 2017 Meeting
  • Int'l Joint Research
• [Presentation] ヒト赤芽球におけるオルガネラリロケーションの統括的制御機構の解明 (2017)
  • Author(s): 後藤樹史
  • Organizer: 第4回 赤血球研究会
• [Presentation] Cdc42 regulates enucleation of human erythroblasts. (2016)
  • Author(s): Kumi Ubukawa, Tatsufumi Goto, Isuzu Kobayashi, Yong-Mei Guo, Ken Asanuma, Naoto Takahashi, Hideki Wakui & Wataru Nunomura.
  • Organizer: The 2016 ASCB Meeting
  • Place of Presentation: San Francisco (USA).
  • Year and Date: 2016-12-03
• [Presentation] ヒト赤血球系細胞におけるα-synuclein の細胞内局在とリン脂質結合 (2016)
  • Author(s): 菅原琴美, 荒木克哉, 浅沼研, 早川枝李, 鵜生川久美, 小林五十鈴, 山下順助, 高橋直人, 涌井秀樹, 澤田賢一, 望月秀樹, 布村渉
  • Organizer: 第36回日本細胞生物学会・日本ケミカルバイオロジー学会第11回年会合同大会
  • Place of Presentation: 京都テルサ （京都市）
  • Year and Date: 2016-06-15
• [Presentation] ヒドロキシクロロキンによる乳酸脱水素酵素の活性阻害と抗腫瘍効果の解析 (2016)
  • Author(s): 後藤樹史, 菅原琴美, 浅沼研, 小林五十鈴, 鵜生川久美, 郭永梅, 高橋直人, 涌井秀樹, 布村渉
  • Organizer: 日本生化学会東北支部会 第82回例会・シンポジウム
  • Place of Presentation: 弘前大学医学部・基礎大講堂（弘前市）
  • Year and Date: 2016-05-21
• [Presentation] 赤芽球におけるα-synuclein の発現と膜結合解析 (2016)
  • Author(s): 菅原琴美, 荒木克哉, 浅沼研, 早川枝李, 鵜生川久美, 小林五十鈴, 山下順助, 高橋直人, 涌井秀樹, 澤田賢一, 望月秀樹, 布村渉
  • Organizer: 日本膜学会第38年会
  • Place of Presentation: 早稲田大学 西早稲田キャンパス63号館 （新宿区）
  • Year and Date: 2016-05-10
• [Presentation] Enucleation is a process dependent on dynein. (2015)
  • Author(s): Kobayashi I
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 金沢市
  • Year and Date: 2015-10-16