Analyses of HAP1/STB functions in regulation of cell-cycle progression and cellular stress responses

• Project/Area Number: 24790196
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Yamaguchi University
• Principal Investigator: FUJINAGA Ryutaro 山口大学, 医学(系)研究科(研究院), 講師 (30335723)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HAP1 / stigmoid body / ストレス / 細胞分裂 / ハンチントン病 / アポトーシス / プロテアソーム

Research Abstract

Huntingtin-associated protein 1 is a core molecule of the cytoplasmic inclusion, stigmoid body (STB). First, we examined cell-cycle dependent change in HAP1 distribution in HAP1-transfected HeLa cells. In interphase, HAP1 formed large-sized STBs. During mitosis, most of the HAP1/STB disappeared but a subset of HAP1 was concentrated at the spindle poles. When cells entered cytokinesis, HAP1 started to form small-sized STB-like inclusion. Next, we examined effect of stress exposures on HAP1/STB morphology in HAP1-transfected immortalized mouse hypothalamic cell line. HAP1 formed typical STBs in most of the stress conditions (e.g., heat shock, ER stress and serum-starvation). However, in proteasome inhibited condition, HAP1 induced cytoplasmic glanulo-reticular clusters instead of STB formation. Now we are analyzing the mechanism of change in HAP1/STB morphology and its biological significance in proteasome-inhibitor-induced apoptosis.

Research Products

• [Presentation] 細胞ストレス負荷による神経細胞質封入体stigmoid bodyの形態変化～プロテアソーム活性の重要性～ (2014)
  • Author(s): 藤永竜太郎,山下由美子,菊池悠次郎,栁井章江,國分啓司,篠田晃
  • Organizer: 第119回日本解剖学会総会・全国学術集会2014
  • Place of Presentation: 下野市(自治医科大学)
• [Presentation] Neuroanatomical distribution of the STB/HAP1-immunoreactive cells in the spinal cord of the adult rat (2014)
  • Author(s): Md Nabiul Islam, Yukio Takeshita, Ryutaro Fujinaga, Akie Yanai, Keiji Kokubu, Ren Yonetani, Mir Rubayet Jahan, Greggoly John Wroblewski, Koh Shinoda
  • Organizer: 第119回日本解剖学会総会・全国学術集会2014
  • Place of Presentation: 下野市(自治医科大学)
• [Presentation] 細胞ストレス負荷による神経細胞質封入体stigmoid bodyの 形態変化～プロテアソーム活性の重要性～ (2014)
  • Author(s): 藤永 竜太郎, 山下 由美子, 菊池 悠次郎, 栁井 章江, 國分 啓司, 篠田 晃
  • Organizer: 第119回 日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医科大学（下野市）
• [Presentation] Neuroanatomical distribution of the STB/HAP1-immunoreactive cells in the spinal cord of the adult rat (2014)
  • Author(s): Md Nabiul Islam, Yukio Takeshita, Ryutaro Fujinaga, Akie Yanai, Keiji Kokubu, Ren Yonetani, Mir Rubayet Jahan, Greggoly John Wroblewski, Koh Shinoda
  • Organizer: 第119回 日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医科大学（下野市）
• [Presentation] 神経細胞特異的封入体の神経変性疾患における役割 (2013)
  • Author(s): 藤永竜太郎
  • Organizer: 山口大学研究推進体「ストレス」成果報告シンポジウム2013
  • Place of Presentation: 宇部市(山口大学)
  • Year and Date: 2013-02-08
• [Presentation] Distribution of the huntingtin-associated protein 1 (HAP1) in the spinal cord of the adult rat (2013)
  • Author(s): M. N. Islam, R. Fujinaga, A. Yanai, K. Kokubu, R. Yonetani, C. Yamada, H. Yoshidome, Y. Kikuchi, M. R. Jahan, K. Shinoda
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego, USA
• [Presentation] Immunohistochemical distribution of the Huntingtin-associated protein 1(HAP1)in the spinal cord of adult rat (2013)
  • Author(s): MD Islam, Ryutaro Fujinaga, Mir R. Jahan, Akie Yanai, Keiji Kokubu, Naoto Hayasaka, Ren Yonetani, Koh Shinoda
  • Organizer: Neuro2013
  • Place of Presentation: 京都市(国立京都国際会館)
• [Presentation] 神経細胞質封入体stigmoid bodyの形態制御に対するプロテアソーム阻害剤の影響 (2013)
  • Author(s): 藤永竜太郎,山下由美子,菊池悠次郎,今井智子,栁井章江,國分啓司,篠田晃
  • Organizer: 第118回日本解剖学会総会・全国学術集会2013
  • Place of Presentation: 高松市(サンポート高松)
• [Presentation] Distribution of the huntingtin-associated protein 1 (HAP1) in the spinal cord of the adult rat. (2013)
  • Author(s): M. N. Islam, R. Fujinaga, A. Yanai, K. Kokubu, R. Yonetani, C. Yamada, H. Yoshidome, Y. Kikuchi, M. R. Jahan, K. Shinoda
  • Organizer: Neuroscience 2013
  • Place of Presentation: サンディエゴ（アメリカ）
• [Presentation] 神経細胞質封入体stigmoid bodyの形態制御に対するプロテアソーム阻害剤の影響 (2013)
  • Author(s): 藤永 竜太郎, 山下 由美子, 菊池 悠次郎, 今井 智子, 栁井 章江, 國分 啓司, 篠田 晃
  • Organizer: 第118回 日本解剖学会総会・全国学術集会
  • Place of Presentation: 高松市（サンポート高松）
• [Presentation] ハンチントン病関連蛋白質(HAP1)が形成する神経細胞質封入体"stigmoid body"の細胞内ダイナミクス (2012)
  • Author(s): 藤永竜太郎
  • Organizer: 第5回研究推進体「ストレス」フォーラム2012
  • Place of Presentation: 宇部市(山口大学)
  • Year and Date: 2012-05-01
• [Presentation] Sporadically lurking Huntingtin-associated protein 1 immunoreactive (SLH) cells in the hippocampus and its morphological relationships with the progenitor cell markers, GABA, and steroid receptors (2012)
  • Author(s): Md. Nabiul Islam, Ryutaro Fujinaga, Akie Yanai, Mir Rubayet Jahan, Keiji Kokubu, Yumiko Yamashita, Tatsuya Watanabe and Koh Shinoda
  • Organizer: 15th International Congress on Hormonal Steroids and Homones & Cancer 2012
  • Place of Presentation: Kanazawa(Ishikawa Ongakudo)
• [Presentation] Immunohistochemical characterization of the"sporadically lurking HAP1-immunoreactive (SLH) cells"in the hippocampus, with special reference to the expression of steroid receptors, g-aminobutyric acid, basket cell and progenitor cell markers (2012)
  • Author(s): M. N. Islam, R. Fujinaga, A. Yanai, M. R. Jahan, Y. Takeshita, K. Kokubu, Y. Yamashita, C. Ishikawa, K. Shinoda
  • Organizer: Neuroscience 2012
  • Place of Presentation: New Orleans, USA
• [Presentation] Sporadically lurking Huntingtin-associated protein 1 immunoreactive (SLH) cells in the hippocampus and its morphological relationships with the progenitor cell markers, GABA, and steroid receptors. (2012)
  • Author(s): Md. Nabiul Islam, Ryutaro Fujinaga, Akie Yanai, Mir Rubayet Jahan, Keiji Kokubu, Yumiko Yamashita, Tatsuya Watanabe and Koh Shinoda
  • Organizer: 15th International Congress on Hormonal Steroids and Homones & Cancer
  • Place of Presentation: 金沢市（石川県立音楽堂）
• [Presentation] Immunohistochemical characterization of the “sporadically lurking HAP1-immunoreactive (SLH) cells” in the hippocampus, with special reference to the expression of steroid receptors, γ-aminobutyric acid, basket cell and progenitor cell markers (2012)
  • Author(s): M. N. Islam, R. Fujinaga, A. Yanai, M. R. Jahan, Y. Takeshita, K. Kokubu, Y. Yamashita, C. Ishikawa, K. Shinoda
  • Organizer: Neuroscience 2012
  • Place of Presentation: New Orleans (USA)