Novel functions of plasmalogens at the cell-cell contact site

• Project/Area Number: 26440102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyushu University
• Principal Investigator: Honsho Masanori 九州大学, 生体防御医学研究所, 特任准教授 (90372747)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: プラスマローゲン / コレステロール / 細胞接着 / 生合成制御 / フリッパーゼ / 細胞間接着 / セルトリ細胞 / 細胞間接着構造 / ペルオキシソーム

Outline of Final Research Achievements

The aim of this study is to uncover novel functions of plasmalogens. I found that plasmalogens are required for the expression of connexin 43, a protein that forms gap junctions in sertoli cells. Moreover, absence of plasmalogens reduces localization of E-cadherin at adherens junctions in MCF7 cells which retain characteristics of differentiated mammary epithelium. Both connexin 43 and E-cadherin are shown to be enriched in lipid rafts, a cholesterol- and sphyngolipid-enriched compartment of the plasma membrane. Analysis of cholesterol synthesis by modulating the cellular level of plasmalogens revealed that homeostasis of plasmalogen is important for the regulation of cholesterol biosynthesis by controlling the stability of squalene monooxygenase, the proposed second rate-limiting enzyme in cholesterol biosynthesis. Together, these results suggest that plasmalogens play important roles in several physiological processes in mammals.

Research Products

• [Journal Article] Reduction of ether-type glycerophospholipids, plasmalogens, by NF-κB signal leading to microglial activation (2017)
  • Author(s): Hossain, Md. S., Abe, Y., Ali, F., Youssef, M., Honsho, M., Fujiki, Y., and *Katafuchi, T.
  • Journal Title: J. Neurosci. Volume: 37 Issue: 15 Pages: 4074-4092
  • DOI: 10.1523/jneurosci.3941-15.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasmalogen synthesis is spatiotemporally regulated by sensing plasmalogens in the inner leaflet of plasma membrane. (2017)
  • Author(s): Honsho, M., Abe, Y., and *Fujiki, Y.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 43936-43936
  • DOI: 10.1038/srep43936
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Defining dynamin-based ring organizing center on the peroxisome-dividing machinery isolated from Cyanidioschyzon merolae. (2017)
  • Author(s): Imoto, Y., Abe, Y., Okumoto, K., Honsho, M., Kuroiwa, H., Kuroiwa, T., and *Fujiki, Y.
  • Journal Title: J. Cell Sci. Volume: 130 Issue: 5 Pages: 853-867
  • DOI: 10.1242/jcs.199182
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peroxisome homeostasis: mechanisms of division and selective degradation of peroxisomes in mammals. (2016)
  • Author(s): Honsho, M., Yamashita,S., and Fujiki, Y.
  • Journal Title: Biochim. Biophys. Acta- Mol. Cell Res. Volume: 1863 Issue: 5 Pages: 984-991
  • DOI: 10.1016/j.bbamcr.2015.09.032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pex11p mediates peroxisomal proliferation by promoting deformation of the lipid membrane. (2015)
  • Author(s): Yoshida, Y., Niwa, H., Honsho, M., Itoyama, A., and Fujiki,Y.
  • Journal Title: Biology Open Volume: 4 Issue: 6 Pages: 910-721
  • DOI: 10.1242/bio.201410801
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis. (2015)
  • Author(s): Honsho, M., Abe, Y., and Fujiki, Y
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 48 Pages: 28822-28833
  • DOI: 10.1074/jbc.m115.656983
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pex11p mediates peroxisomal proliferation by promoting deformation of the lipid membrane (2015)
  • Author(s): Yoshida, Y., Niwa, H., Honsho, M., Itoyama, A., and Fujiki,Y.
  • Journal Title: Biology Open Volume: in press
  • Open Access / Acknowledgement Compliant
• [Journal Article] Mild reduction of plasmalogens causes rhizomelic chondrodysplasia punctata: Functional characterization of a novel mutation (2014)
  • Author(s): Noguchi, M., Honsho, M., Abe, Y., Toyama, R., Niwa, H., Sato, Y., Ghaedi, K., Rahmanifar, A., Shafeghati, Y., and *Fujiki, Y.
  • Journal Title: Journal of Human Genetics Volume: 59 Issue: 7 Pages: 387-392
  • DOI: 10.1038/jhg.2014.39
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] エーテルリン脂質プラスマローゲンの生合成制御機構-プラスマローゲンの感知システム- (2016)
  • Author(s): 本庄雅則、阿部雄一、藤木幸夫
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] Plasmalogen Synthesis Is Spatiotemporally Regulated by Sensing Plasmalogens in the Inner Leaflet of Plasma Membrane (2016)
  • Author(s): Masanori Honsho, Yuichi Abe, and Yukio Fujiki
  • Organizer: The 1st International Plasmalogen Symposium
  • Place of Presentation: 福岡市
  • Year and Date: 2016-11-07
  • Int'l Joint Research
• [Presentation] DHRS7B Targets to Peroxisomes by a PEX19-dependent Class I Pathway (2016)
  • Author(s): Megumi Tanaka, Masanori Honsho, and Yukio Fujiki
  • Organizer: The 1st International Plasmalogen Symposium
  • Place of Presentation: 福岡市
  • Year and Date: 2016-11-07
  • Int'l Joint Research
• [Presentation] Lipidomic Analysis of Fibroblasts from Patients with Peroxisome Biogenesis Deficiency and PEX Gene-Knockout Mouse (2016)
  • Author(s): Yuichi Abe, Masanori Honsho, and Yukio Fujiki
  • Organizer: The 1st International Plasmalogen Symposium
  • Place of Presentation: 福岡市
  • Year and Date: 2016-11-07
  • Int'l Joint Research
• [Presentation] Reduction of Plasmalogens in the Brain Is Associated with Microglial Activation, Stress and Aging (2016)
  • Author(s): Reduction of Plasmalogens in the Brain Is Associated with Microglial Activation, Stress and Aging
  • Organizer: Hossain, Md. S., Yuichi Abe, Y., MaHonsho, M., Ali, F., Youssef, M., Fujiki, Y., and Katafuch, T.
  • Place of Presentation: 福岡市
  • Year and Date: 2016-11-07
  • Int'l Joint Research
• [Presentation] エーテルリン脂質プラスマローゲンの恒常性の生理的意義 (2015)
  • Author(s): 本庄 雅則、阿部雄一、藤木幸夫
  • 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: 神戸ポートアイランド（神戸市）
  • Year and Date: 2015-12-01
• [Presentation] エーテルリン脂質プラスマローゲン依存的なコレステロールの生合成制御 (2015)
  • Author(s): 本庄 雅則 、阿部 雄一 、藤木 幸夫
  • Organizer: 第57回日本脂質生化学会
  • Place of Presentation: 一橋大学一橋講堂（東京都）
  • Year and Date: 2015-06-28
• [Presentation] The role of peroxisomes in lipid metabolism (2015)
  • Author(s): Yukio Fujiki, Yuichi Abe and Masanori Honsho
  • Organizer: This 6th international conference on Phospholipase A2 and Lipid Mediators (PLM2015)
  • Place of Presentation: 東京都
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] D-アミノ酸酸化酵素（DAO)の細胞内局在異常による細胞毒性 (2014)
  • Author(s): 福留久美子、阿部雄一、本庄雅則、藤木幸夫
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] エーテルリン脂質プラスマローゲン依存的なコレステロールの生合成 (2014)
  • Author(s): 本庄雅則, 藤木幸夫
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15 – 2014-10-18
• [Book] Analysis of plasmalogen synthesis in cultured cells. In: Schrader, M. (ed.) Peroxisomes: Methods and Protocols (2017)
  • Author(s): Honsho, M., and Fujiki, Y.
  • Total Pages: 7
  • Publisher: Springer, Humana Press
• [Book] In vitro PMP import analysis using cell-free synthesized PMP and isolated peroxisomes. (2017)
  • Author(s): Liu,Y., Honsho, M., and Fujiki, Y
  • Total Pages: 6
  • Publisher: Springer, Humana Press
• [Book] Peroxisomal membrane and matrix protein import using a semi-intact mammalian cell system. (2017)
  • Author(s): Okumoto, K., Honsho, M., Liu, Y., and Fujiki, Y.
  • Total Pages: 7
  • Publisher: Springer, Humana Press
• [Book] 機能性食品と薬理栄養 Vol. 19 (2016)
  • Author(s): 藤木幸夫、本庄雅則
  • Total Pages: 6
  • Publisher: インフォノーツパブリッシング
• [Book] Encyclopedia of Life Sciences, Protein Import into Peroxisomes: the principles and methods of studying (version 2.0). (2015)
  • Author(s): Fujiki, Y., Okumoto, K., and Honsho, M.
  • Publisher: John Wiley & Sons, Chichester, UK,
• [Book] 医学のあゆみ Vol. 254 (2015)
  • Author(s): 藤木幸夫、奥本寛治、本庄雅則
  • Total Pages: 5
  • Publisher: 医歯薬出版
• [Book] Encyclopedia of Life Sciences (2015)
  • Author(s): Fujiki, Y., Okumoto, K., and Honsho.
  • Publisher: John Wiley & Sons, Chichester, UK