Mechanisms of large cargoes secretion

• Project/Area Number: 26440046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: SAITO KOTA 東京大学, 大学院薬学系研究科(薬学部), 助教 (60549632)
• Co-Investigator(Renkei-kenkyūsha): KATADA TOSHIAKI 武蔵野大学, 薬学部, 教授 (10088859)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 分泌 / 小胞体 / コラーゲン / ER exit site / COPII / 低分子量Gタンパク質

Outline of Final Research Achievements

The mechanisms of collagen secretion have not been well characterized, because collagens synthesized within the ER are too large to fit into conventional COPII-coated vesicles. We previously characterized TANGO1 as a collagen cargo receptor. In this study, we have characterized that TANGO1 forms macromolecular complexes with cTAGE5 and TANGO1. In addition, we have revealed that TANGO1 acts as a scaffold in corporation with Sec16 and functions as an organizer of ER exit site. We have also identified Sec23a as a protein up-regulated during hepatic stellate cell activation. When Sec23a is depleted, activation of hepatic stellate cells is attenuated.

Research Products

• [Int'l Joint Research] UC Berkeley(米国)
• [Journal Article] Regulation of the Sar1 GTPase Cycle Is Necessary for Large Cargo Secretion from the Endoplasmic Reticulum (2017)
  • Author(s): Saito Kota、Maeda Miharu、Katada Toshiaki
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 5 Pages: 75-75
  • DOI: 10.3389/fcell.2017.00075
  • Peer Reviewed / Open Access
• [Journal Article] CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport (2017)
  • Author(s): Tomoishi Shotaro、Fukushima Shinichi、Shinohara Kentaro、Katada Toshiaki、Saito Kota
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 7992-7992
  • DOI: 10.1038/s41598-017-08703-6
  • Peer Reviewed / Open Access
• [Journal Article] Remodeling of ER‐exit sites initiates a membrane supply pathway for autophagosome biogenesis (2017)
  • Author(s): Ge Liang、Zhang Min、Kenny Samuel J、Liu Dawei、Maeda Miharu、Saito Kota、Mathur Anandita、Xu Ke、Schekman Randy
  • Journal Title: EMBO reports Volume: 18 Issue: 9 Pages: 1586-1603
  • DOI: 10.15252/embr.201744559
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TANGO1 recruits Sec16 to coordinately organize ER exit sites for efficient secretion (2017)
  • Author(s): Maeda Miharu、Katada Toshiaki、Saito Kota
  • Journal Title: The Journal of Cell Biology Volume: 216 Issue: 6 Pages: 1731-1743
  • DOI: 10.1083/jcb.201703084
  • Peer Reviewed
• [Journal Article] Dual function of cTAGE5 in collagen export from the endoplasmic reticulum. (2016)
  • Author(s): Tanabe, T., Maeda, M., Saito, K., and Katada, T.
  • Journal Title: Mol. Biol. Cell Volume: 27 Issue: 13 Pages: 2008-2013
  • DOI: 10.1091/mbc.e16-03-0180
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Distinct isoform-specific complexes of TANGO1 cooperatively facilitate collagen secretion from the endoplasmic reticulum. (2016)
  • Author(s): Maeda, M., Saito, K., and Katada, T.
  • Journal Title: Mol. Biol. Cell Volume: 27 Issue: 17 Pages: 2688-2696
  • DOI: 10.1091/mbc.e16-03-0196
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mechanisms for exporting large-sized cargoes from the endoplasmic reticulum. (2015)
  • Author(s): Saito K, Katada T.
  • Journal Title: Cell Mol. Life Sci. Volume: 72 Issue: 19 Pages: 3709-3720
  • DOI: 10.1007/s00018-015-1952-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export. (2014)
  • Author(s): Saito K, Yamashiro K, Shimazu N, Tanabe T, Kontani K, Katada T.
  • Journal Title: Journal of Cell Biology Volume: 206 (6) Issue: 6 Pages: 751-762
  • DOI: 10.1083/jcb.201312062
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 高等真核生物に特有な分泌機構全般の解明 (2017)
  • Author(s): 齋藤 康太
  • Organizer: ConBio2017
  • Invited
• [Presentation] Mechanisms of secretion by ER-resident macromolecular complex. (2017)
  • Author(s): Kota Saito
  • Organizer: 1st International Symposium on Cell Logistics at GIST
  • Int'l Joint Research / Invited
• [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 (2017)
  • Author(s): 齋藤康太、前田深春、佐々木紀人、友石章太郎、堅田利明
  • Organizer: 第16回生命科学研究会
• [Presentation] 小胞体からのコラーゲン分泌機構の解析 (2016)
  • Author(s): 齋藤康太、前田深春、篠原健太郎、佐々木紀人、友石章太郎、堅田利明
  • Organizer: 第６８回日本細胞生物学会大会
  • Place of Presentation: 京都テルサ（京都府京都市）
  • Year and Date: 2016-06-16
• [Presentation] Mechanisms of collagen secretion from the endoplasmic reticulum. (2015)
  • Author(s): Kota Saito
  • Organizer: 第31回国際生物学賞シンポジウム
  • Place of Presentation: 京都国際会館 (京都府・京都市)
  • Year and Date: 2015-12-05
  • Int'l Joint Research / Invited
• [Presentation] 生理的および肝線維化時におけるコラーゲン分泌機構の解析 (2015)
  • Author(s): 齋藤 康太、前田 深春、篠原 健太朗、堅田 利明．
  • Organizer: BMB2015 第38回日本分子生物学会年会第88回日本生化学会大会合同年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-03
  • Int'l Joint Research / Invited
• [Presentation] Mechanisms of collagen secretion from the endoplasmic reticulum. (2015)
  • Author(s): Kota Saito
  • Organizer: Chinese Academy of Sciences
  • Place of Presentation: 北京（中華人民共和国）
  • Year and Date: 2015-09-25
  • Invited
• [Presentation] Mechanisms of collagen secretion from the endoplasmic reticulum. (2015)
  • Author(s): Kota Saito
  • Organizer: Peking University
  • Place of Presentation: 北京（中華人民共和国）
  • Year and Date: 2015-09-24
  • Invited
• [Presentation] Dual function of cTAGE5 in collagen export from the ER. (2015)
  • Author(s): Kota Saito, Tomoya Tanabe, Toshiaki Katada.
  • Organizer: Gordon Research Conference, Molecular membrane biology
  • Place of Presentation: Andover（米国）
  • Year and Date: 2015-07-15
  • Int'l Joint Research
• [Presentation] コラーゲン分泌に対しcTAGE5は２種の異なる機能を有する (2015)
  • Author(s): 齋藤 康太、田辺 共哉、篠原 健太郎、前田 深春、佐々木 紀人、堅田 利明．
  • Organizer: 第67回日本細胞生物学会
  • Place of Presentation: タワーホール船堀（東京都・江戸川区）
  • Year and Date: 2015-06-30
• [Presentation] 小胞体からのコラーゲン分泌機構の機能解析 (2015)
  • Author(s): 齋藤 康太、篠原 健太郎、前田 深春、佐々木 紀人、友石 章太郎、堅田 利明．
  • Organizer: 第14回生命科学研究会
  • Place of Presentation: 三浦市民ホール（神奈川県・三浦市）
  • Year and Date: 2015-06-26
• [Presentation] 肝線維化におけるコラーゲン分泌機構の解析 (2014)
  • Author(s): 福島 槙一、前田 深春、齋藤 康太、堅田 利明
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館・グランドプリンスホテル京都(京都府・京都市)
  • Year and Date: 2014-10-18
• [Presentation] 肝星細胞活性化に伴う分泌動態変化の解析 (2014)
  • Author(s): 齋藤 康太、福島 槙一、前田 深春、堅田 利明
  • Organizer: 第22回肝細胞研究会
  • Place of Presentation: 東京医科歯科大学 (東京都・文京区)
  • Year and Date: 2014-06-28
• [Presentation] 新奇Ｇサイクルの起動制御に関わる構造生物学的解析 (2014)
  • Author(s): 堅田 利明、齋藤 康太．
  • Organizer: 新学術領域研究「構造細胞生物学」班会議
  • Place of Presentation: ルスツリゾートホテル（北海道・虻田郡留寿都村）
  • Year and Date: 2014-06-14
• [Presentation] 生理的および肝線維化時におけるコラーゲン分泌機構の解析 (2014)
  • Author(s): 齋藤 康太、福島 槙一、篠原 健太郎、田辺 共哉、平塚 允乃、前田 深春、堅田 利明
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良新公会堂、東大寺総合文化センター(奈良県・奈良市)
  • Year and Date: 2014-06-11
• [Remarks] 東京大学大学院薬学系研究科生理化学教室
  • URL: http://www.f.u-tokyo.ac.jp/~seiri/