Nagasato Ayaka Ichikawa, Yamashita Hiroshi, Matsuo Michinori, Ueda Kazumitsu, Kioka Noriyuki
a Division of Applied Life Sciences, Graduate School of Agriculture , Kyoto University , Kyoto , Japan.
b Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University , Kyoto , Japan.
Biosci Biotechnol Biochem. 2017 Jun;81(6):1136-1147. doi: 10.1080/09168451.2017.1289074. Epub 2017 Feb 13.
Extracellular matrix (ECM) stiffness regulates cell differentiation, survival, and migration. Our previous study has shown that the interaction of the focal adhesion protein vinculin with vinexin α plays a critical role in sensing ECM stiffness and regulating stiffness-dependent cell migration. However, the mechanism how vinculin-vinexin α interaction affects stiffness-dependent cell migration is unclear. Lipid rafts are membrane microdomains that are known to affect ECM-induced signals and cell behaviors. Here, we show that vinculin and vinexin α can localize to lipid rafts. Cell-ECM adhesion, intracellular tension, and a rigid ECM promote vinculin distribution to lipid rafts. The disruption of lipid rafts with Methyl-β-cyclodextrin impaired the ECM stiffness-mediated regulation of vinculin behavior and rapid cell migration on rigid ECM. These results indicate that lipid rafts play an important role in ECM-stiffness regulation of cell migration via vinculin.
细胞外基质（ECM）硬度调节细胞分化、存活和迁移。我们之前的研究表明，粘着斑蛋白纽蛋白与葡萄球菌蛋白α的相互作用在感知ECM硬度和调节硬度依赖性细胞迁移中起关键作用。然而，纽蛋白-葡萄球菌蛋白α相互作用如何影响硬度依赖性细胞迁移的机制尚不清楚。脂筏是已知会影响ECM诱导信号和细胞行为的膜微区。在这里，我们表明纽蛋白和葡萄球菌蛋白α可以定位于脂筏。细胞-ECM粘附、细胞内张力和刚性ECM促进纽蛋白向脂筏的分布。用甲基-β-环糊精破坏脂筏会损害ECM硬度介导的纽蛋白行为调节以及细胞在刚性ECM上的快速迁移。这些结果表明，脂筏在通过纽蛋白进行的ECM硬度调节细胞迁移中起重要作用。
