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Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics

Author

Listed:
  • Kaori Kanemaru

    (Tokyo University of Science)

  • Makoto Shimozawa

    (Tokyo University of Pharmacy and Life Sciences)

  • Manabu Kitamata

    (Tokyo University of Pharmacy and Life Sciences)

  • Rikuto Furuishi

    (Tokyo University of Science)

  • Hinako Kayano

    (Tokyo University of Pharmacy and Life Sciences)

  • Yui Sukawa

    (Tokyo University of Pharmacy and Life Sciences)

  • Yuuki Chiba

    (Tokyo University of Pharmacy and Life Sciences)

  • Takatsugu Fukuyama

    (Tokyo University of Pharmacy and Life Sciences)

  • Junya Hasegawa

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Hiroki Nakanishi

    (Akita University
    Lipidome Lab Co., Ltd)

  • Takuma Kishimoto

    (Hokkaido University Graduate School of Life Science)

  • Kazuya Tsujita

    (Kobe University
    Kobe University Graduate School of Medicine)

  • Kazuma Tanaka

    (Hokkaido University Graduate School of Life Science)

  • Toshiki Itoh

    (Kobe University
    Kobe University Graduate School of Medicine)

  • Junko Sasaki

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Takehiko Sasaki

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Kiyoko Fukami

    (Tokyo University of Pharmacy and Life Sciences)

  • Yoshikazu Nakamura

    (Tokyo University of Science)

Abstract

Epithelial cells provide cell-cell adhesion that is essential to maintain the integrity of multicellular organisms. Epithelial cell-characterizing proteins, such as epithelial junctional proteins and transcription factors are well defined. However, the role of lipids in epithelial characterization remains poorly understood. Here we show that the phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is enriched in the plasma membrane (PM) of epithelial cells. Epithelial cells lose their characteristics upon depletion of PM PI(4,5)P2, and synthesis of PI(4,5)P2 in the PM results in the development of epithelial-like morphology in osteosarcoma cells. PM localization of PARD3 is impaired by depletion of PM PI(4,5)P2 in epithelial cells, whereas expression of the PM-targeting exocyst-docking region of PARD3 induces osteosarcoma cells to show epithelial-like morphological changes, suggesting that PI(4,5)P2 regulates epithelial characteristics by recruiting PARD3 to the PM. These results indicate that a high level of PM PI(4,5)P2 plays a crucial role in the maintenance of epithelial characteristics.

Suggested Citation

  • Kaori Kanemaru & Makoto Shimozawa & Manabu Kitamata & Rikuto Furuishi & Hinako Kayano & Yui Sukawa & Yuuki Chiba & Takatsugu Fukuyama & Junya Hasegawa & Hiroki Nakanishi & Takuma Kishimoto & Kazuya Ts, 2022. "Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30061-9
    DOI: 10.1038/s41467-022-30061-9
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    References listed on IDEAS

    as
    1. Kaori Kanemaru & Yoshikazu Nakamura & Kojiro Sato & Ryota Kojima & Saori Takahashi & Mami Yamaguchi & Manabu Ichinohe & Hiroshi Kiyonari & Go Shioi & Kenji Kabashima & Kyoko Nakahigashi & Masataka Asa, 2012. "Epidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    2. Christian J Gröger & Markus Grubinger & Thomas Waldhör & Klemens Vierlinger & Wolfgang Mikulits, 2012. "Meta-Analysis of Gene Expression Signatures Defining the Epithelial to Mesenchymal Transition during Cancer Progression," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-10, December.
    3. Syed Mukhtar Ahmed & Ian G. Macara, 2017. "The Par3 polarity protein is an exocyst receptor essential for mammary cell survival," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    4. Junko Sasaki & Satoshi Kofuji & Reietsu Itoh & Toshihiko Momiyama & Kiyohiko Takayama & Haruka Murakami & Shinsuke Chida & Yuko Tsuya & Shunsuke Takasuga & Satoshi Eguchi & Ken Asanuma & Yasuo Horie &, 2010. "The PtdIns(3,4)P2 phosphatase INPP4A is a suppressor of excitotoxic neuronal death," Nature, Nature, vol. 465(7297), pages 497-501, May.
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