Morphological and functional analyses of phosphatases of the lipid second messenger in the neurons, pancreas and adrenal gland

• Project/Area Number: 17K08507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Akita University
• Principal Investigator: Hozumi Yasukazu 秋田大学, 医学系研究科, 教授 (00372334)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ジアシルグリセロールキナーゼ / 免疫組織化学染色 / 特異抗体 / 結合タンパク質 / イノシトール三リン酸受容体 / ゴルジ体 / 小胞体 / 虚血ストレス / 免疫沈降法 / 海馬 / 線条体 / 大脳皮質 / 投射ニューロン / 介在ニューロン / 免疫電子顕微鏡法 / 内在性カンナビノイド

Outline of Final Research Achievements

Analysis of the localization of DGKepsilon (DGKe) in the central nervous system revealed that DGKe was expressed in hippocampus, cerebral cortex and striatal projection neurons, but not in interneurons. We also newly reported that DGKzeta (DGKz) localizes to the nuclei of outer hair cells in the cochlea and translocates from the nucleus to the cytoplasm by acoustic stimulation. It was revealed that DGKgamma (DGKg) is localized in the Golgi apparatus and DGKe is expressed in the endoplasmic reticulum in zona glomerulosa cells of the adrenal gland. The abundant expression of DGK isozymes in the peripheral organs as well as central nervous system and the localization changes upon external stimulation suggest that this enzyme may have an important role in cell function.

Academic Significance and Societal Importance of the Research Achievements

脂質性二次伝達物質ジアシルグリセロールのリン酸化酵素であるジアシルグリセロールキナーゼ（DGK）ファミリーのうち、イプシロン型DGK（DGKe）の神経細胞と内分泌器官である副腎における発現および細胞内微細局在が明らかになった。また、DGKeが小脳においてイノシトール三リン酸受容体と免疫複合体を形成することを形態学的に明らかにした。DGKeの抑制がハンチントン舞踏病の治療に有効である可能性が報告されており、当研究成果がハンチントン舞踏病の発症メカニズムや病態解明の一助となることが期待される。

Research Products

• [Journal Article] Knockdown of DEAD-box RNA helicase DDX5 selectively attenuates serine 311 phosphorylation of NF-κB p65 subunit and expression level of anti-apoptotic factor Bcl-2. (2020)
  • Author(s): Tanaka K, Tanaka T*, Nakano T, Hozumi Y, Yanagida M, Araki Y, Iwazaki K, Takagi M, Goto K
  • Journal Title: Cellular Signalling Volume: 65 Pages: 1-8
  • DOI: 10.1016/j.cellsig.2019.109428
  • Peer Reviewed
• [Journal Article] Nucleosome assembly proteins NAP1L1 and NAP1L4 modulate p53 acetylation to regulate cell fate. (2019)
  • Author(s): Tanaka T, Hozumi Y, Martelli AM, Iino M, Goto K
  • Journal Title: BBA Molecular Cell Research Volume: 1866 Issue: 12 Pages: 1-13
  • DOI: 10.1016/j.bbamcr.2019.118560
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] DzMab-1: Anti-Human Diacylglycerol Kinaseζ Monoclonal Antibody for Immunocytochemistry. (2019)
  • Author(s): Nakano T, Ogasawara S, Tanaka T, Hozumi Y, Sano M, Sayama Y, Yamada S, Shirai Y, Kaneko MK, Kato Y, Goto K
  • Journal Title: Monoclonal antibodies in immunodiagnosis and immunotherapy Volume: 38 Issue: 4 Pages: 179-182
  • DOI: 10.1089/mab.2019.0024
  • Peer Reviewed
• [Journal Article] Expression and localization of diacylglycerol kinase ζ in guinea pig cochlea and its functional implication under noise-exposure stress conditions (2019)
  • Author(s): Shinkawa C, Ito T, Hozumi Y, Chiba M, Matsui H, Goto K, Kakehata S
  • Journal Title: Histochem Cell Biol. Volume: epub Issue: 6 Pages: 461-474
  • DOI: 10.1007/s00418-019-01781-9
  • Peer Reviewed
• [Journal Article] DgMab-6: Antihuman DGKgamma Monoclonal Antibody for Immunocytochemistry. (2018)
  • Author(s): Nakano T, Ogasawara S, Tanaka T, Hozumi Y, Yamaki A, Sakane F, Shirai Y, Nakamura T, Yanaka M, Yamada S, Kaneko MK, Kato Y, Goto K.
  • Journal Title: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Volume: 37 Issue: 5 Pages: 229-232
  • DOI: 10.1089/mab.2018.0026
  • Peer Reviewed
• [Presentation] 下垂体中間葉細胞におけるベータ型ジアシルグリセロールキナーゼの情報伝達系 (2018)
  • Author(s): 八月朔日 泰和
  • Organizer: 第123回 日本解剖学会総会・全国学術集会