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质膜磷脂酰肌醇（4,5）-二磷酸对上皮特征的决定至关重要。

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

机构信息

Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.

Laboratory of Genome and Biosignals, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.

出版信息

Nat Commun. 2022 May 9;13(1):2347. doi: 10.1038/s41467-022-30061-9.

DOI:10.1038/s41467-022-30061-9
PMID:35534464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9085759/
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)P] is enriched in the plasma membrane (PM) of epithelial cells. Epithelial cells lose their characteristics upon depletion of PM PI(4,5)P, and synthesis of PI(4,5)P 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)P 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)P regulates epithelial characteristics by recruiting PARD3 to the PM. These results indicate that a high level of PM PI(4,5)P plays a crucial role in the maintenance of epithelial characteristics.

摘要

上皮细胞提供细胞间黏附，这对于维持多细胞生物的完整性至关重要。上皮细胞特征蛋白，如上皮连接蛋白和转录因子，已得到很好的定义。然而，脂质在上皮特征化中的作用仍知之甚少。本文作者表明，磷脂酰肌醇（4,5）-二磷酸[PI（4,5）P]在上皮细胞的质膜（PM）中富集。PM PI（4,5）P 耗竭会导致上皮细胞失去特征，而 PM 中 PI（4,5）P 的合成会导致骨肉瘤细胞呈现上皮样形态。在上皮细胞中，PM PI（4,5）P 的耗竭会损害 PARD3 的 PM 定位，而 PARD3 的 PM 靶向外泌体 docking 区的表达会诱导骨肉瘤细胞发生上皮样形态变化，表明 PI（4,5）P 通过将 PARD3 募集到 PM 来调节上皮特征。这些结果表明，PM PI（4,5）P 的高水平对于维持上皮特征至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/fb6365beafb7/41467_2022_30061_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/0de3f9172251/41467_2022_30061_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/7003606b6b13/41467_2022_30061_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/e120fb3b4e3a/41467_2022_30061_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/0fa8e9757b00/41467_2022_30061_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/8581e473a146/41467_2022_30061_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/923fe10d7317/41467_2022_30061_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/fb6365beafb7/41467_2022_30061_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/0de3f9172251/41467_2022_30061_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/7003606b6b13/41467_2022_30061_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/e120fb3b4e3a/41467_2022_30061_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/0fa8e9757b00/41467_2022_30061_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/8581e473a146/41467_2022_30061_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/923fe10d7317/41467_2022_30061_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b184/9085759/fb6365beafb7/41467_2022_30061_Fig7_HTML.jpg

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