Functional analysis of novel membrane complexes involved in collagen secretion and ERES formation

• Project/Area Number: 17H03651
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Akita University
• Principal Investigator: Saito Kota 秋田大学, 医学系研究科, 教授 (60549632)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 分泌 / ER exit site / Sec16 / TANGO1 / コラーゲン / 小胞体 / キナーゼ / 細胞生物学

Outline of Final Research Achievements

How ER exit sites disassemble during mitosis was not well understood. We revealed that TANGO1, a cargo receptor originally identified for collagens, acts as a core for ER exit site disassembly. We revealed that TANGO1 is phosphorylated by Casein Kinase 1 and dephosphorylated by Protein Phosphatase 1.

Academic Significance and Societal Importance of the Research Achievements

我々は、細胞分裂期においてもERESが崩壊しない状態を作り出すことに成功した。これによって細胞分裂を停止することができれば、新たな抗がん剤の標的となりうる。

Research Products

• [Int'l Joint Research] University of Oslo(ノルウェー)
• [Int'l Joint Research] Ludwig-Maximilians-Universitat(ドイツ)
• [Int'l Joint Research] Warsaw University of Life Sciences(ポーランド)
• [Int'l Joint Research] Lund University(スウェーデン)
• [Int'l Joint Research] University of Oslo(ノルウェー)
• [Int'l Joint Research] Ludwig-Maximilians-Universitat(ドイツ)
• [Int'l Joint Research] Warsaw University of Life Sciences(ポーランド)
• [Journal Article] Mitotic ER Exit Site Disassembly and Reassembly Are Regulated by the Phosphorylation Status of TANGO1 (2020)
  • Author(s): Maeda Miharu、Komatsu Yukie、Saito Kota
  • Journal Title: Developmental Cell Volume: 55 Issue: 2 Pages: 237-250.e5
  • DOI: 10.1016/j.devcel.2020.07.017
  • NAID: 130008001624
  • Peer Reviewed
• [Journal Article] Mitotic ER exit site dynamics: insights into blockade of secretion from the ER during mitosis (2020)
  • Author(s): Maeda Miharu、Komatsu Yukie、Saito Kota
  • Journal Title: Molecular & Cellular Oncology Volume: 7 Issue: 6 Pages: 1832420-1832420
  • DOI: 10.1080/23723556.2020.1832420
  • Peer Reviewed
• [Journal Article] LTK is an ER-resident receptor tyrosine kinase that regulates secretion (2019)
  • Author(s): Centonze Federica G.、Reiterer Veronika、Nalbach Karsten、Saito Kota、Pawlowski Krzysztof、Behrends Christian、Farhan Hesso
  • Journal Title: Journal of Cell Biology Volume: 218 Issue: 8 Pages: 2470-2480
  • DOI: 10.1083/jcb.201903068
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Not just a cargo receptor for large cargoes; an emerging role of TANGO1 as an organizer of ER exit sites (2019)
  • Author(s): Saito Kota、Maeda Miharu
  • Journal Title: The Journal of Biochemistry Volume: 166 Issue: 2 Pages: 115-119
  • DOI: 10.1093/jb/mvz036
  • NAID: 40021974856
  • Peer Reviewed / Open Access
• [Journal Article] COPII proteins exhibit distinct subdomains within each ER exit site for executing their functions (2019)
  • Author(s): Maeda Miharu、Kurokawa Kazuo、Katada Toshiaki、Nakano Akihiko、Saito Kota
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 7346-7346
  • DOI: 10.1038/s41598-019-43813-3
  • NAID: 120007169371
  • Peer Reviewed / Open Access
• [Journal Article] The binding of TBK1 to STING requires exocytic membrane traffic from the ER (2018)
  • Author(s): Ogawa Emari、Mukai Kojiro、Saito Kota、Arai Hiroyuki、Taguchi Tomohiko
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 503 Issue: 1 Pages: 138-145
  • DOI: 10.1016/j.bbrc.2018.05.199
  • Peer Reviewed
• [Presentation] 細胞分裂期における分泌停止メカニズムの解明 (2021)
  • Author(s): 前田 深春、小松 幸恵、齋藤 康太
  • Organizer: 第94回日本薬理学会年会
• [Presentation] Mitotic ER exit site dissociation and reassembly are regulated by phosphorylation status of TANGO1 (2019)
  • Author(s): Maeda,M., Komatsu, Y., Saito, K.
  • Organizer: Gordon Research Conferences, Molecular Membrane Biology
  • Int'l Joint Research
• [Presentation] cTAGE5 acts as a Sar1 GTPase regulator for collagen export (2019)
  • Author(s): Maeda, M.,Sasaki,N., Shiraiwa, M., Yorimitsu, T., Sato, K., Katada, T., Saito, K.
  • Organizer: Gordon Research Conferences, Molecular Membrane Biology
  • Int'l Joint Research
• [Presentation] 巨大分子の分泌機構 (2019)
  • Author(s): 齋藤 康太
  • Organizer: 第61回日本先天代謝異常学会総会・第17回アジア先天代謝異常症シンポジウム
  • Invited
• [Presentation] 細胞周期に応じたリン酸化による分泌調節機構 (2019)
  • Author(s): 前田 深春、小松 幸恵、齋藤 康太
  • Organizer: 第70回日本薬理学会北部会,
• [Presentation] 細胞周期に応じた小胞体出芽ゾーン「ERES」の崩壊と再形成の分子機構 (2019)
  • Author(s): 齋藤 康太
  • Organizer: 第3回オルガネラ・ゾーン研究会
• [Presentation] Evolutionary Perspective on the ER exit sites structure (2018)
  • Author(s): 齋藤 康太
  • Organizer: 第70回 日本細胞生物学会 第51回 日本発生生物学会 合同大会
• [Presentation] Phosphorylation of TANGO1 regulates localization and function of ER exit sites (2018)
  • Author(s): 前田 深春、堅田 利明、齋藤 康太
  • Organizer: 第70回 日本細胞生物学会 第51回 日本発生生物学会 合同大会
• [Presentation] 巨大分子の分泌機構 (2018)
  • Author(s): 齋藤 康太
  • Organizer: 2018年度 日本生化学会関東支部例会
  • Invited
• [Presentation] TANGO1はSec16と協調的にER exit siteの形成制御機構に関与する (2018)
  • Author(s): 前田 深春、齋藤 康太
  • Organizer: 第17回 生命科学研究会
• [Presentation] 小胞体出芽ドメイン形成の種間保存性と相違性について (2018)
  • Author(s): 齋藤 康太、前田 深春、小松 幸恵
  • Organizer: 第69回 薬理学会北部会
• [Presentation] Mechanisms of Secretion in Fibrosis (2018)
  • Author(s): Kota Saito
  • Organizer: American Society for Matrix Biology
  • Int'l Joint Research / Invited
• [Presentation] Regulation of the Sar1 GTPase cycle is necessary for collagen secretion from the endoplasmic reticulum (2018)
  • Author(s): Miharu Maeda, Kota Saito
  • Organizer: American Society for Matrix Biology
  • Int'l Joint Research
• [Presentation] 小胞体出芽部位(ER exit site)構造の進化的保存性と多様性について (2018)
  • Author(s): 齋藤 康太
  • Organizer: 第41回 日本分子生物学会年会
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/department/gs/kenkyu-org/kouza/yakuri.html
• [Remarks] 秋田大学大学院医学系研究科 情報制御学・実験治療学講座
  • URL: https://www.med.akita-u.ac.jp/department/gs/kenkyu-org/kouza.php?koza=yakuri