Role of binding of plectin to the integrin β4 subunit in the assembly of hemidesmosomes
Role of binding of plectin to the integrin β4 subunit in the assembly of hemidesmosomes
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DOI：
10.1091/mbc.e03-09-0697
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Sonnenberg, A
中科院分区：
文献类型：
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作者：
Koster, J;van Wilpe, S;Sonnenberg, A
我们之前已经证明，通过其肌动蛋白结合结构域（ABD）与第一对纤维连接蛋白III型（FNIII）重复序列和整合素β 4亚基的一小部分连接片段（残基1328-1355）的结合，plectin被募集到半染色体体中。在这里，我们发现两个脯氨酸残基（P1330和P1333）在连接段的这一区域对支持β - 4介导的粘附素募集至关重要。在生化和酵母双杂交实验中发现了β 4上plakin结构域的其他结合位点。这些位点位于连接片段的末端（残基1383-1436）和包含第四个FNIII重复和c尾的区域（残基1570-1752）。然而，在细胞中，如果没有凝集素- abd与β - a4的相互作用，这些额外的结合位点不能诱导半粒酶体的组装。由于额外的plectin结合位点与介导beta4细胞质结构域分子内结合的序列重叠，我们认为它们不能被结合，需要作为plectin- abd与beta4结合的结果暴露出来。此外，这些额外的结合位点可能是定位β 4细胞质结构域以与其他半粒染色体组分最佳相互作用所必需的，从而提高半粒染色体组装的效率。
We have previously shown that plectin is recruited into hemidesmosomes through association of its actin-binding domain (ABD) with the first pair of fibronectin type III (FNIII) repeats and a small part of the connecting segment (residues 1328-1355) of the integrin beta4 subunit. Here, we show that two proline residues (P1330 and P1333) in this region of the connecting segment are critical for supporting beta4-mediated recruitment of plectin. Additional binding sites for the plakin domain of plectin on beta4 were identified in biochemical and yeast two-hybrid assays. These sites are located at the end of the connecting segment (residues 1383-1436) and in the region containing the fourth FNIII repeat and the C-tail (residues 1570-1752). However, in cells, these additional binding sites cannot induce the assembly of hemidesmosomes without the interaction of the plectin-ABD with beta4. Because the additional plectin binding sites overlap with sequences that mediate an intramolecular association of the beta4 cytoplasmic domain, we propose that they are not accessible for binding and need to become exposed as the result of the binding of the plectin-ABD to beta4. Furthermore, these additional binding sites might be necessary to position the beta4 cytoplasmic domain for an optimal interaction with other hemidesmosomal components, thereby increasing the efficiency of hemidesmosome assembly.