Analysis of molecular mechanism and physiological functions of the stress-responsive nucleocytoplasmic transport mediated by Hikeshi

• Project/Area Number: 26440109
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kose Shingo 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員 (90333278)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 核-細胞質間輸送 / 熱ストレス / 分子シャペロン / Hikeshi / Hsp70 / 熱ショックストレス

Outline of Final Research Achievements

Nuclear import of molecular chaperone HSP70 under heat-stress conditions is mediated by a nucleocytoplasmic transport carrier, Hikeshi. This study revealed that V54L point-mutation in Hikeshi gene is associated with a severe hereditary disease. These results suggest that Hikeshi is likely to have important role(s) not only under heat-stress conditions, but also in various cellular situations. Further, we reported the crystal structure of Hikeshi. These studies provided insights into new mechanism and functions of the Hikeshi-mediated transport.

Research Products

• [Int'l Joint Research] Chungbuk National University(韓国)
• [Int'l Joint Research] Hadassah Medical Center(イスラエル)
• [Journal Article] Extensive cargo identification reveals distinct biological roles of the 12 Importin pathways (2017)
  • Author(s): Kimura, M., Morinaka, Y., Imai, K., Kose, S, Horton, P, Imamoto, N
  • Journal Title: eLife Volume: 6
  • DOI: 10.7554/elife.21184
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene (2016)
  • Author(s): Edvardson,S., Kose,S., Jalas, C., Fattal-Valevski,A., Watanabe, A., Ogawa, Y., Mamada, H., Fedick, A.M., Ben-Shachar, S., Treff, N.R., Shaag, A.,Bale, S., Gärtner, J., Imamoto, N., Elpeleg, O.
  • Journal Title: J. Med. Genet. Volume: 53 Issue: 2 Pages: 132-137
  • DOI: 10.1136/jmedgenet-2015-103232
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells (2015)
  • Author(s): Shrestha, R., Tatsukawa, H., Shrestha, R., Ishibashi, N., Matsuura, T., Kagechika, H., Kose, S., Hitomi, K., Imamoto, N., Kojima S.
  • Journal Title: Cell Death. Dis. Volume: 6 Issue: 12 Pages: e2002-e2002
  • DOI: 10.1038/cddis.2015.339
  • Peer Reviewed / Open Access
• [Journal Article] Structural and functional analysis of Hikeshi, a new nuclear transport receptor of Hsp70s. (2015)
  • Author(s): Song J, Kose S, Watanabe A, Son SY, Choi S, Hong H, Yamashita E, Park IY, Imamoto N, Lee SJ.
  • Journal Title: Acta Crystallogr D Biol Crystallogr. Volume: 71 Issue: 3 Pages: 473-483
  • DOI: 10.1107/s1399004714026881
  • Peer Reviewed
• [Journal Article] Reconstitution of nucleocytoplasmic transport using digitonin-permeabilized cells (2015)
  • Author(s): Kose, S., Funakoshi, T., Imamoto, N.
  • Journal Title: Methods Mol. Biol. Volume: 1262 Pages: 291-303
  • DOI: 10.1007/978-1-4939-2253-6_18
  • ISBN: 9781493922529, 9781493922536
• [Journal Article] Analysis of nucleocytoplasmic transport in digitonin-permeabilized cells under different cellular conditions (2014)
  • Author(s): Furuta, M., Kose, S., Kehlenbach, R.H., Imamoto, N.
  • Journal Title: Methods Cell Biol. Volume: 122 Pages: 331-352
  • DOI: 10.1016/b978-0-12-417160-2.00015-1
• [Journal Article] Nucleocytoplasmic transport under stress conditions and its role in HSP70 chaperone systems (2014)
  • Author(s): Kose, S., Imamoto, N.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1840 Issue: 9 Pages: 2953-2960
  • DOI: 10.1016/j.bbagen.2014.04.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Schizosaccharomyces pombe Hikeshi/Opi10 protein has similar biochemical functions to its human homolog but acts in different physiological contexts. (2014)
  • Author(s): Oda, Y., Kimura, M., Kose, S., Fasken, M.B., Corbett, A.H., Imamoto, N.
  • Journal Title: FEBS Lett. Volume: 印刷中 Issue: 10 Pages: 304-4
  • DOI: 10.1016/j.febslet.2014.04.018
  • Peer Reviewed
• [Presentation] Hikeshiノックアウト細胞における遺伝子発現変化とストレス応答の解析 (2017)
  • Author(s): 小瀬真吾、渡邊愛、高木昌俊、儘田博志、今本尚子
  • Organizer: 第34回染色体ワークショップ・第15回核ダイナミクス研究会合同開催
  • Place of Presentation: かずさアカデミアホール(千葉県木更津市)
  • Year and Date: 2017-01-11
• [Presentation] 核-細胞質間タンパク質運搬体分子Hikeshi: 熱ストレス時に活性化する分子シャペロンHSP70輸送機構とその生理機能 (2016)
  • Author(s): 小瀬真吾、今本尚子
  • Organizer: 第89回日本生化学会大会 シンポジウム「温度生物学の新展開」
  • Place of Presentation: 東北大学川内キャンパス(宮城県仙台市)
  • Year and Date: 2016-09-25
  • Invited
• [Presentation] 核-細胞質間輸送運搬体Hikeshiの機能：熱ストレス応答時における遺伝子発現変化の網羅的解析 (2016)
  • Author(s): 小瀬真吾、高木昌俊、儘田博志、今本尚子
  • Organizer: 第33回染色体ワークショップ・第14回核ダイナミクス研究会合同開催
  • Place of Presentation: 宮城県宮城郡(松島一の坊)
  • Year and Date: 2016-01-12
• [Presentation] 熱ストレス依存的HSP70運搬体分子Hikeshi：その機能と遺伝性疾患 (2015)
  • Author(s): 小瀬真吾、渡邊愛、今本尚子
  • Organizer: 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大会
  • Place of Presentation: 神戸市(神戸ポートアイランド)
  • Year and Date: 2015-12-02
• [Presentation] HSP70輸送分子Hikeshi：その構造と機能 (2015)
  • Author(s): 小瀬真吾、Jinsue Song、渡邊愛、Soo Jae Lee、今本尚子
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京都江戸川区(タワーホール船堀)
  • Year and Date: 2015-07-01
• [Presentation] HSP70分子シャペロンシステムにおける核-細胞質間運搬体分子Hikeshiの機能解析 (2014)
  • Author(s): 小瀬真吾、渡邊愛、儘田博志、高木昌俊、今本尚子
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市(国立京都国際会館)
  • Year and Date: 2014-10-18
• [Presentation] 分子シャペロンHSP70運搬体分子Hikeshiの輸送機構とその機能解析 (2014)
  • Author(s): 小瀬真吾、亀高愛、渡邊愛、本橋詳子、今本尚子
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良市(奈良県新公会堂)
  • Year and Date: 2014-06-11
• [Presentation] Hikeshiによる熱ストレス依存的HSP70核内移行 (2014)
  • Author(s): 小瀬真吾
  • Organizer: 理研シンポジウム「細胞システムの動態と論理 VI」
  • Place of Presentation: 和光市(理研)
  • Year and Date: 2014-04-03 – 2014-04-04
• [Book] 生化学 (2015)
  • Author(s): 小瀬真吾
  • Publisher: 日本生化学会