Understanding functional structure of dynein complexes/clusters required for mitotic spindle assembly and positioning

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02481
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: Kiyomitsu Tomomi 沖縄科学技術大学院大学, 細胞分裂動態ユニット, 准教授 (10503443)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 紡錘体 / ダイニン / オーキシン誘導デグロン / メダカ / NuMA

Outline of Final Research Achievements

In this project, we aim to understand the functional structure and its regulations of dynein complexes/clusters during mitosis by combining auxin-inducible degron, biochemical purification, and mass spectrometry. Regarding human cell projects, we succeeded in analyzing AID-dependent depletion phenotype in dynein, dynactin or other dynein-binding partner depleted conditions. In addition, we succeeded in purifying mitotic dynein complexes and its modifications using mass spectrometry. Importantly, we found that NuMA depletion causes chromosome missegregation via checkpoint-insensitive k-fiber minus-end detachment from mitotic spindle poles (van Toorn et al., Current Biology 2023). We are additionally preparing two research papers. Regarding medaka fish project, we published a paper which characterizes spindle assembly processes in medaka early embryos (Kiyomitsu et al, Nature Communications 2024).

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて、ヒト細胞において紡錘体の極収束異常は、チェックポイントに感知されずに染色体の分配異常につながるという、新しい概念を提唱することができた。また本研究成果は、分裂期のダイニン複合体の機能や複合体形成、紡錘体形成、配置制御機構を理解する上で必須の知見を提供する。また脊椎動物の初期胚におけるダイニン複合体の細胞内動態や機能はこれまでほとんど解析されておらず、新たな知見となり、哺乳類を含む動物の初期胚分裂やその異常の理解に貢献できる可能性がある。