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

Kaori Kanemaru, Makoto Shimozawa, Manabu Kitamata, Rikuto Furuishi, Hinako Kayano, Yui Sukawa, Yuuki Chiba, Takatsugu Fukuyama, Junya Hasegawa, Hiroki Nakanishi, Takuma Kishimoto, Kazuya Tsujita, Kazuma Tanaka, Toshiki Itoh, Junko Sasaki, Takehiko Sasaki, Kiyoko Fukami () and Yoshikazu Nakamura ()
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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
Hiroki Nakanishi: Akita University
Takuma Kishimoto: Hokkaido University Graduate School of Life Science
Kazuya Tsujita: Kobe University
Kazuma Tanaka: Hokkaido University Graduate School of Life Science
Toshiki Itoh: Kobe University
Junko Sasaki: Tokyo Medical and Dental University
Takehiko Sasaki: Tokyo Medical and Dental University
Kiyoko Fukami: Tokyo University of Pharmacy and Life Sciences
Yoshikazu Nakamura: Tokyo University of Science

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30061-9

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