Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan; Department of Emergency and Disaster Medicine, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
Biochem Biophys Res Commun. 2019 May 7;512(3):429-434. doi: 10.1016/j.bbrc.2019.03.027. Epub 2019 Mar 14.
Integrins on exosomes have been shown to mediate binding to recipient cells, potentially playing important roles in controlling exosomal internalization and organ distributions. Although the ability of cellular integrins to mediate cell adhesion is known to be regulated by the cytoplasmic adaptor protein talin, whether the activity of exosomal integrins is similarly regulated by talin remains to be elucidated. Here we have studied this question in T-cell exosomes that surface express the integrins αLβ2 and α4β7. T-cells and T-cell exosomes engineered to lack talin-2 showed reduced binding to the integrin ligand ICAM-1 and MAdCAM-1 compared with control T-cells and exosomes, despite the fact that those T cells and exosomes express intact levels of the other isoform talin-1. In addition, talin-2-deficient T-cell exosomes were less efficiently internalized by endothelial cells, compared with control exosomes. These results suggest that the mechanisms of talin-mediated integrin regulation operate similarly in cells and exosomes.
外泌体上的整合素已被证明介导与受体细胞的结合，可能在控制外泌体内化和器官分布中发挥重要作用。尽管细胞整合素介导细胞黏附的能力已知受到细胞质衔接蛋白 talin 的调节，但外泌体整合素的活性是否同样受到 talin 的调节仍有待阐明。在这里，我们研究了在表面表达整合素 αLβ2 和 α4β7 的 T 细胞外泌体中的这个问题。与对照 T 细胞和外泌体相比，缺乏 talin-2 的 T 细胞和经工程改造缺乏 talin-2 的 T 细胞外泌体与整合素配体 ICAM-1 和 MAdCAM-1 的结合减少，尽管这些 T 细胞和外泌体表达完整水平的另一种同工型 talin-1。此外，与对照外泌体相比，talin-2 缺陷型 T 细胞外泌体被内皮细胞内化的效率较低。这些结果表明，talin 介导的整合素调节的机制在细胞和外泌体中相似。
