Sonnenberg A
The Netherlands Cancer Institute, Division of Cell Biology, Amsterdam.
Curr Top Microbiol Immunol. 1993;184:7-35. doi: 10.1007/978-3-642-78253-4_2.
Integrins are expressed on almost every cell type and are responsible for the linkage of the extracellular matrix with the cytoskeleton. In this review I have focused on the intra- and extracellular proteins that bind to integrins. Although many integrins bind to the same extracellular ligand, they mostly recognize different sites on these ligands. Some integrins interact with the same site but then there are requirements for different additional sequences to obtain high affinity. By modulating the expression and activity of integrins in the plasma membrane, cells can adapt their capacity of binding to the matrix. How integrins become activated is as yet not clear, but interaction with other proteins or lipids may be critical. Binding to ligands could also be modulated by alternative splicing of mRNAs for ligand binding sites in the extracellular domain. In Drosophila, the mRNA for the extracellular domain of the PS2 integrin is spliced near a site implicated in ligand binding. In humans, however, there are no indications that alternative splicing contributes to the regulation of function of the extracellular domain of integrins. The only splice variant of the extracellular domain of an integrin identified so far concerns are alpha subunit of the alpha IIb beta 3 complex, but the splicing occurs in a region that has not been implicated in cell adhesion. There is also no evidence as yet that integrin function can be modulated by alternative splicing of mRNA for the cytoplasmic domain of integrin subunits. However, the loss of function seen with some deletion mutants of the cytoplasmic domains of integrin subunits suggests that such a mechanism may well exist. In a different way the binding capacity of a given cell can be influenced by regulating the expression of its ligand or by alternative mRNA splicing of sequences encoding the cell binding domain in their ligands. In the case of fibronectin, the mRNA for one of the integrin binding sites is subject to alternative splicing. The mRNAs for the three chains of laminin appear not to be subject to alternative splicing but, by combining different variant chains of laminin, isoforms can be generated which may have different affinities for integrins. Binding of cells to the matrix therefore does not only depend on the expression and activity of the correct integrin but also of the correct variant of the ligand.(ABSTRACT TRUNCATED AT 400 WORDS)
整合素几乎在每种细胞类型上都有表达，负责细胞外基质与细胞骨架的连接。在这篇综述中，我重点关注了与整合素结合的细胞内和细胞外蛋白质。尽管许多整合素与相同的细胞外配体结合，但它们大多识别这些配体上的不同位点。一些整合素与相同位点相互作用，但随后需要不同的附加序列来获得高亲和力。通过调节整合素在质膜中的表达和活性，细胞可以调整其与基质结合的能力。整合素如何被激活尚不清楚，但与其他蛋白质或脂质的相互作用可能至关重要。与配体的结合也可能通过细胞外结构域中配体结合位点的mRNA可变剪接来调节。在果蝇中，PS2整合素细胞外结构域的mRNA在一个与配体结合有关的位点附近进行剪接。然而，在人类中，没有迹象表明可变剪接有助于整合素细胞外结构域功能的调节。到目前为止，唯一确定的整合素细胞外结构域的剪接变体涉及αIIbβ3复合物的α亚基，但剪接发生在一个与细胞黏附无关的区域。也没有证据表明整合素功能可以通过整合素亚基细胞质结构域的mRNA可变剪接来调节。然而，整合素亚基细胞质结构域的一些缺失突变体所表现出的功能丧失表明这种机制很可能存在。以不同的方式，给定细胞的结合能力可以通过调节其配体的表达或通过其配体中编码细胞结合结构域的序列的可变mRNA剪接来影响。就纤连蛋白而言，整合素结合位点之一的mRNA会发生可变剪接。层粘连蛋白三条链的mRNA似乎不会发生可变剪接，但通过组合层粘连蛋白的不同变体链，可以产生对整合素具有不同亲和力的异构体。因此，细胞与基质的结合不仅取决于正确整合素的表达和活性，还取决于配体的正确变体。（摘要截断于400字）
