Phosphatidylinositol 4,5-bisphosphate is localized in the plasma membrane outer leaflet and regulates cell adhesion and motility
Phosphatidylinositol 4,5-bisphosphate is localized in the plasma membrane outer leaflet and regulates cell adhesion and motility
复制标题
磷脂酰肌醇 4,5-二磷酸位于质膜外叶，调节细胞粘附和运动
DOI：
10.1016/j.bbrc.2020.05.040
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Fukami K.
中科院分区：
文献类型：
--
作者：
Yoneda A.;Kanemaru K.;Matsubara A.;Takai E.;Shimozawa M.;Satow R.;Yamaguchi H.;Nakamura Y.;Fukami K.
磷脂不对称地分布在哺乳动物细胞的质膜（PM）中。磷脂酰肌醇 (PI) 及其磷酸化形式主要位于 PM 的内叶中。其中，磷脂酰肌醇4,5-二磷酸（PI(4,5)P2）是众所周知的磷脂酶C（PLC）或磷酸肌醇3激酶的底物，也是肌动蛋白细胞骨架或离子通道的调节剂。尽管 PI(4,5)P2 在内部小叶中的功能已得到很好的表征，但对外部小叶中的功能却知之甚少。此处，通过抗 PI(4,5)P2 抗体和特异性结合 PI(4,5)P2 的 PLCδ1 的 pleckstrin 同源 (PH) 结构域，在非透化细胞的细胞表面检测到 PI(4,5)P2。在各种细胞系和新鲜分离的小鼠骨髓细胞中普遍检测到细胞表面PI(4,5)P2信号，并以胆固醇、鞘磷脂和肌动蛋白聚合依赖性方式显示点状模式。此外，通过添加抗PI(4,5)P2抗体或PLCδ1的PH结构域来阻断细胞表面PI(4,5)P2可抑制细胞附着、扩散和迁移。综上所述，这些结果表明 PI(4,5)P2 在外叶中的独特定位可能在细胞附着、扩散和迁移中发挥关键作用。
Phospholipids are distributed asymmetrically in the plasma membrane (PM) of mammalian cells. Phosphatidylinositol (PI) and its phosphorylated forms are primarily located in the inner leaflet of the PM. Among them, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a well-known substrate for phospholipase C (PLC) or phosphoinositide-3 kinase, and is also a regulator for the actin cytoskeleton or ion channels. Although functions of PI(4,5)P2in the inner leaflet are well characterized, those in the outer leaflet are poorly understood. Here, PI(4,5)P2was detected in the cell surface of non-permeabilized cells by anti-PI(4,5)P2antibodies and the pleckstrin-homology (PH) domain of PLCδ1 that specifically binds PI(4,5)P2. Cell surface PI(4,5)P2signal was universally detected in various cell lines and freshly isolated mouse bone marrow cells and showed a punctate pattern in a cholesterol, sphingomyelin, and actin polymerization-dependent manner. Furthermore, blocking cell surface PI(4,5)P2by the addition of anti-PI(4,5)P2antibody or the PH domain of PLCδ1 inhibited cell attachment, spreading, and migration. Taken together, these results indicate a unique localization of PI(4,5)P2in the outer leaflet that may have a crucial role in cell attachment, spreading, and migration.