TOWARD A GENETIC-ANALYSIS OF CELL-MATRIX ADHESION
TOWARD A GENETIC-ANALYSIS OF CELL-MATRIX ADHESION
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DOI：
10.1101/sqb.1992.057.01.030
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发表时间：
1992-01-01
期刊：
影响因子：
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通讯作者：
YANG, JT
中科院分区：
文献类型：
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作者：
HYNES, RO;GEORGE, EL;YANG, JT
细胞与其相邻细胞以及细胞外基质的相互作用在发育以及许多生理和病理过程中起着至关重要的作用（Hay 1991; Hynes and Lander 1992）。在过去的十多年中，对细胞粘附的研究已经揭示了大量细胞粘附分子的存在。这些包括参与细胞-细胞粘附的细胞表面受体，如钙粘蛋白（Takeichi 1988，1990，1991）、免疫球蛋白超家族成员（Peguell 1988; Grumet 1991）和选择素（贝维拉夸et al. 1991; Lasky and罗森1992）。这些受体家族中的每一个都包括多个相关分子。对于细胞-基质粘附也是如此，其最常由称为整联蛋白的粘附受体家族介导（Hynes 1987，1992; Albelda和Buck 1990; Hemler 1990）。整联蛋白是异二聚体跨膜受体，其大的细胞外结构域与细胞外基质的粘附分子或与其它细胞上的反受体相互作用，以介导细胞粘附。它们较小的胞质结构域与细胞骨架相互作用，也参与信号转导过程（Shattil和Brugge 1991; Hynes 1992）。整联蛋白家族是非常多样的（表1），虽然每种整联蛋白在其结合的配体中显示出选择性，但存在两种简并性。首先，许多整联蛋白结合几种不同的配体。第二，大多数细胞外基质蛋白可以被多种整合素识别。图1显示了两种粘附性细胞外基质分子（层粘连蛋白和纤维蛋白原）。大多数细胞表达多种整合素，因此能够与细胞外基质分子相互作用，具有相当大的通用性。几种整合素亚基可以以选择性剪接的形式存在，这一事实增加了进一步的复杂性（见表1中的序列）。在脊椎动物整联蛋白的情况下，这种选择性剪接仅已知影响胞质结构域，在那里它被认为调节与细胞骨架和/或信号转导事件的相互作用。然而，在果蝇中，至少两个整合素亚基可以在其胞外结构域中选择性剪接，在分子的靠近配体结合和/或亚基相互作用位点的区域中
The interactions of cells with their neighbors and with the extracetlular matrix play crucial roles in development and in numerous physiological and pathological processes (Hay 1991; Hynes and Lander 1992). Studies of cell adhesion during the past decade and more have uncovered the existence of a large number of cell adhesion molecules. These include cellsurface receptors involved in cell-cell adhesion, such as the cadherins (Takeichi 1988, 1990, 1991), members of the immunoglobulin superfamily (Jessell 1988; Grumet 1991), and selectins (Bevilacqua et al. 1991; Lasky and Rosen 1992). Each of these families of receptors includes multiple related molecules. The same is true for cell-matrix adhesion, which is most frequently mediated by the family of adhesion receptors known as integrins (Hynes 1987, 1992; Albelda and Buck 1990; Hemler 1990).Integrins are heterodimeric transmembrane receptors whose large extracellular domains interact with adhesive molecules of the extracellular matrix, or with counterreceptors on other cells, to mediate cell adhesion. Their smaller cytoplasmic domains interact with the cytoskeleton and are also involved in signal transduction processes (Shattil and Brugge 1991; Hynes 1992). The integrin family is very diverse (Table 1), and although each integrin shows selectivity in the ligands it binds, there is degeneracy of two kinds. First, many integrins bind several different ligands. Second, most extracellular matrix proteins can be recognized by multiple integrins. This is diagramed for two adhesive extracellular matrix molecules (laminin and fibrinogen) in Figure 1. Most cells express multiple integrins and are, therefore, able to interact with extracellular matrix molecules with considerable versatility. Further complexity is added by the fact that several integrin subunits can occur in alternatively spliced forms (see asterisks in Table 1). In the case of vertebrate integrins, this alternative splicing is only known to affect the cytoplasmic domains, where it is thought to modulate interactions with the cytoskeleton and/or signal transduction events. However, in Drosophila, at least two integrin subunits can be alternatively spliced in their extracellular domains, in regions of the molecules close to the ligand-binding and/or subunit interaction sites