Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland.
Q Rev Biophys. 2019 Nov 11;52:e10. doi: 10.1017/S0033583519000088.
Integrins are large heterodimeric type 1 membrane proteins expressed in all nucleated mammalian cells. Eighteen α-chains and eight β-chains can combine to form 24 different integrins. They are cell adhesion proteins, which bind to a large variety of cellular and extracellular ligands. Integrins are required for cell migration, hemostasis, translocation of cells out from the blood stream and further movement into tissues, but also for the immune response and tissue morphogenesis. Importantly, integrins are not usually active as such, but need activation to become adhesive. Integrins are activated by outside-in activation through integrin ligand binding, or by inside-out activation through intracellular signaling. An important question is how integrin activity is regulated, and this topic has recently drawn much attention. Changes in integrin affinity for ligand binding are due to allosteric structural alterations, but equally important are avidity changes due to integrin clustering in the plane of the plasma membrane. Recent studies have partially solved how integrin cell surface structures change during activation. The integrin cytoplasmic domains are relatively short, but by interacting with a variety of cytoplasmic proteins in a regulated manner, the integrins acquire a number of properties important not only for cell adhesion and movement, but also for cellular signaling. Recent work has shown that specific integrin phosphorylations play pivotal roles in the regulation of integrin activity. Our purpose in this review is to integrate the present knowledge to enable an understanding of how cell adhesion is dynamically regulated.
整合素是一种大型异二聚体 I 型跨膜蛋白，存在于所有有核哺乳动物细胞中。18 种α链和 8 种β链可以组合形成 24 种不同的整合素。它们是细胞黏附蛋白，与多种细胞内和细胞外配体结合。整合素对于细胞迁移、止血、细胞从血流中移出并进一步进入组织的迁移、免疫反应和组织形态发生是必需的。重要的是，整合素通常不是以活性形式存在，而是需要激活才能具有黏附性。整合素通过整合素配体结合的外向激活或通过细胞内信号的内向激活而被激活。一个重要的问题是整合素活性如何被调节，这个话题最近引起了广泛关注。整合素对配体结合的亲和力的变化是由于变构结构的改变，但同样重要的是由于整合素在质膜平面上的聚集导致的亲合力的改变。最近的研究部分解决了整合素细胞表面结构在激活过程中如何变化的问题。整合素胞质结构域相对较短，但通过与多种细胞质蛋白以调节方式相互作用，整合素获得了许多不仅对细胞黏附和运动，而且对细胞信号转导都很重要的特性。最近的工作表明，特定的整合素磷酸化在整合素活性的调节中起着关键作用。我们在这篇综述中的目的是整合目前的知识，以了解细胞黏附是如何动态调节的。
