Regulatory mechanism of transcription by ciliary proteins.

• Project/Area Number: 19H03447
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kagawa University (2021); Hokkaido University (2019-2020)
• Principal Investigator: Suizu Futoshi 香川大学, 医学部, 准教授 (90431379)
• Co-Investigator(Kenkyū-buntansha): 徳光 浩 岡山大学, ヘルスシステム統合科学学域, 教授 (20237077) ; 平田 徳幸 北海道大学, 遺伝子病制御研究所, その他 (40595956) ; 松岡 達臣 高知大学, 教育研究部自然科学系理工学部門, 教授 (90209510)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 一次繊毛 / 転写 / シスト / 細胞極性 / 平面内細胞極性 / 転写活性調節 / 形態形成 / 繊毛虫 / 繊毛タンパク / 転写制御 / Inversin / 嚢胞腎 / 転写調節

Outline of Research at the Start

本申請研究期間において、繊毛タンパクInversinの転写制御因子としての新規生物機能を証明したい。また、その成果を皮切りに、繊毛タンパク群が直接繊毛から核へ移行し転写制御因子として機能する生物機能の存在を仮説提唱し証明するための核内繊毛タンパクの探索を行いたい。将来的には、転写制御活性をもつ繊毛タンパク群の動態を時空間マッピング化し、生物の形づくりにおいて、繊毛タンパクによる転写調節機構の役割を明らかにするとともに、その破綻によって惹起される繊毛病などの疾病発症の分子メカニズム解明を目指す考えである。

Outline of Final Research Achievements

Inversin accumulates in a Cajal body-like structure in the nucleus, which is one of the centers of transcriptional activity, and has a specific transcriptional regulatory activity. This strongly suggests that the ciliary protein Inversin functions as a novel transcriptional regulator. In addition, it was clarified that during the induction of cyst formation in the unicellular ciliate Colpoda cucullus, rapid fragmentation and expression change of the ciliate constituent protein beta-tubulin occurred and it was taken up into the body. From the dynamic changes of ciliary proteins, it is considered that the localization, structure, and functional changes of ciliary proteins and reabsorption lead to the reuse of amino acids and nucleic acids for cyst formation. In addition, it is presumed that changes in the transcriptional control function of ciliary proteins are important because they acquire the properties of low temperature, low pH, and UV resistance with the rapid change to cysts.

Academic Significance and Societal Importance of the Research Achievements

細胞性一次繊毛は、外界の環境変化を素早く感知し生物反応するための重要な細胞器官である。そのため様々な増殖因子受容体やイオンチャネルなどの重要なタンパク複合体が繊毛特異的に蓄積され、繊毛は細胞内へのシグナル伝達のハブとして機能する。本研究の目的である繊毛タンパクが転写因子として直接機能することを明らかにすることで、細胞の迅速な生物反応と恒常性、増殖、分化制御における繊毛の生物機能の分子メカニズムを解明出来ると考える。本研究成果により、一次繊毛機能の破綻が惹起する繊毛病やがんなどの疾患新規診断・治療法開発へつながり、基礎生物学から臨床研究への波及効果が期待できる。

Research Products

• [Journal Article] Conformation-Dependent Reversible Interaction of Ca2+/Calmodulin-Dependent Protein Kinase Kinase with an Inhibitor, TIM-063 (2022)
  • Author(s): Satomi Ohtsuka;Taisei Okumura;Yuna Τabuchi;Tomoyuki Miyagawa;Naoki Kanayama;Masaki Magari;Naoya Hatano;Hiroyuki Sakagami;Futoshi Suizu;Teruhiko Ishikawa;Hiroshi Tokumitsu
  • Journal Title: Biochemistry Volume: 61(7) Issue: 7 Pages: 545-553
  • DOI: 10.1021/acs.biochem.1c00796
  • Peer Reviewed
• [Journal Article] 土壌繊毛虫コルポーダの陸上環境への適応戦略:休眠シスト形成とその環境ストレス耐性 (2021)
  • Author(s): 十亀陽一郎, 島野智之, 松岡光, 有川幹彦, 水津太, 松岡達臣
  • Journal Title: 原生生物 Volume: 4(1) Pages: 5-14
  • Peer Reviewed
• [Journal Article] Analysis of Water-Soluble Proteins by Two-Dimensional Electrophoresis in the Encystment Process of Colpoda cucullus Nag-1 and Cytoskeletal Dynamics (2021)
  • Author(s): Sogame Yoichiro、Kojima Katsuhiko、Takeshita Toshikazu、Kikuchi Shiho、Shimada Yuto、Nakamura Rikiya、Arikawa Mikihiko、Miyata Seiji、Kinoshita Eiji、Suizu Futoshi、Matsuoka Tatsuomi
  • Journal Title: Acta Protozoologica Volume: 59 Issue: 3-4 Pages: 107-120
  • DOI: 10.4467/16890027ap.20.009.13264
  • Peer Reviewed / Open Access
• [Journal Article] Tolerance of Colpoda cucullus Nag-1 Resting Cysts and Presumed Structure for Protection against UV Light. (2020)
  • Author(s): Yamane S, Watanabe M, Funadani R, Miyazaki R, Hasegawa Y, Arikawa M, Suizu F, Matsuoka K, and Matsuoka T
  • Journal Title: Acta Protozoologica Volume: 59 Issue: 1 Pages: 55-60
  • DOI: 10.4467/16890027ap.20.004.12160
  • Peer Reviewed
• [Journal Article] Antifreeze Water-Rich Dormant Cysts of the Terrestrial Ciliate Colpoda cucullusNag-1 at －65 ˚C: Possible Involvement of Ultra-Antifreeze Polysaccharides (2020)
  • Author(s): Tatsuomi MATSUOKA , Yoichiro SOGAME , Rikiya NAKAMURA , Yuya HASEGAWA , Mikihiko ARIKAWA , Futoshi SUIZU
  • Journal Title: Acta Protozoologica Volume: 59 Issue: 3-4 Pages: 141-147
  • DOI: 10.4467/16890027ap.20.011.13266
  • Peer Reviewed
• [Journal Article] Development and Characterization of Novel Molecular Probes for Ca2+/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609. (2020)
  • Author(s): Ohtsuka S, Ozeki Y, Fujiwara M, Miyagawa T, Kanayama N, Magari M, Hatano N, Suizu F, Ishikawa T, and Tokumitsu H.
  • Journal Title: Biochemistry Volume: 59(17) Issue: 17 Pages: 1701-1710
  • DOI: 10.1021/acs.biochem.0c00149
  • NAID: 120007027579
  • Peer Reviewed / Open Access
• [Journal Article] Tolerance of Colpoda cucullus Nag-1 wet resting cysts to extreme pH (pH 1 and 13): Implications of less permeability of the cyst membrane to H+ and OH (2020)
  • Author(s): Nakamura R, Sogame Y, Arikawa M, Suizu F, and Matsuoka T.
  • Journal Title: The Journal of protozoology research Volume: 30 Issue: 1-2 Pages: 38-46
  • DOI: 10.24556/00004711
  • URL: https://obihiro.repo.nii.ac.jp/records/4729
  • Peer Reviewed
• [Journal Article] Chlorophyllin on Encystment Suppression and Excystment Induction in Colpoda Cucullus NAG-1: An Implication of Chlorophyllin Receptor. (2020)
  • Author(s): Morishita M, Arikawa M, Suizu F, and Matsuoka T.
  • Journal Title: Asian Journal of Microbiology, Biotechnology and Environmental Science Volume: 22(4) Pages: 573-578
  • Peer Reviewed