Molecular Medicine Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.; Department of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
Molecular Medicine Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
J Biol Chem. 2012 Mar 23;287(13):10316-10324. doi: 10.1074/jbc.M111.244962. Epub 2012 Jan 23.
Integrin signaling and membrane blebbing modulate cell adhesion, spreading, and migration. However, the relationship between integrin signaling and membrane blebbing is unclear. Here, we show that an integrin-ligand interaction induces both membrane blebbing and changes in membrane permeability. Sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are membrane proteins located on the bleb membrane. Inhibition of NHE1 disrupts membrane blebbing and decreases changes in membrane permeability. However, inhibition of NCX1 enhances cell blebbing; cells become swollen because of NHE1 induced intracellular sodium accumulation. Our study found that NHE1 induced sodium influx is a driving force for membrane bleb growth, while sodium efflux (and calcium influx) induced by NCX1 in a reverse mode results in membrane bleb retraction. Together, these findings reveal a novel function for NHE1 and NCX1 in membrane blebbing and permeability, and establish a link between membrane blebbing and integrin signaling.
整合素信号转导和细胞膜起泡调节细胞黏附、铺展和迁移。然而，整合素信号转导与细胞膜起泡之间的关系尚不清楚。在这里，我们表明整合素-配体相互作用诱导细胞膜起泡和膜通透性变化。钠-氢交换体 1（NHE1）和钠-钙交换体 1（NCX1）是位于起泡膜上的膜蛋白。NHE1 的抑制破坏了细胞膜起泡并降低了膜通透性的变化。然而，NCX1 的抑制增强了细胞起泡；由于 NHE1 诱导的细胞内钠积累，细胞变得肿胀。我们的研究发现，NHE1 诱导的钠离子内流是膜泡生长的驱动力，而 NCX1 以反向模式诱导的钠离子外排（和钙离子内流）导致膜泡回缩。总之，这些发现揭示了 NHE1 和 NCX1 在细胞膜起泡和通透性中的新功能，并建立了细胞膜起泡与整合素信号转导之间的联系。
