Adherens junctions influence tight junction formation via changes in membrane lipid composition.

How adherens junctions (AJs) influence tight junction (TJ) formation in epithelial cells is unclear. Shigetomi et al. show that loss of AJs affects plasma membrane (PM) lipid composition and that cholesterol addition in α-catenin–knockouts rescues TJ formation. In total, their data suggest that AJs affect TJ formation by controlling PM lipid levels. Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depends on the preceding formation of adherens junctions (AJs) in epithelial cells; however, the underlying mechanism remains to be elucidated. In this study, loss of AJs in α-catenin–knockout (KO) EpH4 epithelial cells altered the lipid composition of the plasma membrane (PM) and led to endocytosis of claudins, a major component of TJs. Sphingomyelin with long-chain fatty acids and cholesterol were enriched in the TJ-containing PM fraction. Depletion of cholesterol abolished the formation of TJs. Conversely, addition of cholesterol restored TJ formation in α-catenin–KO cells. Collectively, we propose that AJs mediate the formation of TJs by increasing the level of cholesterol in the PM.

黏附连接（AJs）如何影响上皮细胞中紧密连接（TJs）的形成尚不清楚。Shigetomi等人表明，AJs的缺失会影响质膜（PM）的脂质组成，并且在α-连环蛋白敲除细胞中添加胆固醇可挽救TJ的形成。总体而言，他们的数据表明AJs通过控制PM脂质水平来影响TJ的形成。 紧密连接（TJs）是重要的细胞黏附结构，在多细胞生物中作为屏障将内部环境与外部环境分隔开。尽管其主要成分已被确定，但TJ的形成是如何被调控的仍不清楚。在上皮细胞中，TJ的形成依赖于先前黏附连接（AJs）的形成；然而，潜在机制仍有待阐明。在这项研究中，α - 连环蛋白敲除（KO）的EpH4上皮细胞中AJs的缺失改变了质膜（PM）的脂质组成，并导致紧密连接的主要成分克劳丁蛋白的内吞作用。含有长链脂肪酸的鞘磷脂和胆固醇在含有TJ的PM组分中富集。胆固醇的缺失会消除TJ的形成。相反，添加胆固醇可恢复α - 连环蛋白敲除细胞中TJ的形成。总之，我们提出AJs通过增加PM中胆固醇的水平来介导TJ的形成。