THE SIZE OF THE INTRACELLULAR BETA-1-INTEGRIN PRECURSOR POOL REGULATES MATURATION OF BETA-1-INTEGRIN SUBUNIT AND ASSOCIATED ALPHA-SUBUNITS
THE SIZE OF THE INTRACELLULAR BETA-1-INTEGRIN PRECURSOR POOL REGULATES MATURATION OF BETA-1-INTEGRIN SUBUNIT AND ASSOCIATED ALPHA-SUBUNITS
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DOI：
10.1042/bj3000771
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发表时间：
1994-06-15
影响因子：
4.1
通讯作者：
LARJAVA, H
中科院分区：
文献类型：
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作者：
KOIVISTO, L;HEINO, J;LARJAVA, H
大量的前体β1-整合素亚基经常在细胞内被发现。在恶变过程中，这个池经常消失。同时，整合素介导的细胞黏附功能受到干扰，即使没有观察到细胞表面β1整合素受体的数量变化。在这里，我们研究了细胞内的前β1整合素池的作用，通过构建产生β1整合素亚单位的反义RNA的载体，将其导入人MG-63骨肉瘤细胞。稳定表达β1-整合素反义RNA的细胞克隆显示，细胞内前β1-整合素亚单位池减少。与未转染组或载体转染组相比，反义转染组细胞β1整合素链的合成减少了65%。β1-整合素链的合成减少与β1-整合素链的加速成熟有关(反义转染细胞的半成熟时间约为5h，而对照细胞约为10.5h)，而α-整合素链的成熟则减慢。然而，细胞表面的β1整合素的数量保持不变。前β1-整合素亚基相对数量下降最大的细胞克隆也显示出整合素功能改变。他们被发现可以合成纤维连接蛋白，但无法将其组装成细胞表面的纤维连接蛋白基质。因此，我们得出结论，抑制β1-整合素链的生物合成导致受体成熟的改变，并可能与受体功能改变有关。
A large pool of precursor beta 1-integrin subunits is frequently found intracellularly. During malignant transformation this pool often disappears. Concomitantly, integrin-mediated cell-adhesion functions are disturbed, even though no change in the number of beta 1-integrin receptors on the cell surface can be observed. Here, we have studied the role of an intracellular pre beta 1-integrin pool by transfecting human MG-63 osteosarcoma cells with plasmid construction producing an antisense RNA for the beta 1-integrin subunit. Stable cell clones expressing beta 1-integrin antisense RNA were shown to have a reduced intracellular pool of pre-beta 1-integrin subunits. In the antisense-transfected cells, the synthesis of the beta 1-integrin chain was reduced by 65% compared with non-transfected or vector-transfected MG-63 cells. The decreased synthesis of the beta 1-integrin chain was associated with accelerated maturation of the beta 1-integrin chain (half-maturation time about 5 h in antisense-transfected cells compared with about 10.5 h in control cells), whereas maturation of the alpha-integrin chain slowed down. The amount of beta 1-integrins on the cell surface, however, remained unaltered. Cell clones with the largest decrease in the relative amount of the pre-beta 1-integrin subunit also showed altered integrin function. They were found to synthesize fibronectin, but were unable to assemble it into a fibronectin matrix on the cell surface. Thus we conclude that the repression of biosynthesis of the beta 1-integrin chain leads to alterations in receptor maturation and may be connected with altered receptor function.