Functional differences between kindlin-1 and kindlin-2 in keratinocytes
Functional differences between kindlin-1 and kindlin-2 in keratinocytes
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DOI：
10.1242/jcs.096214
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发表时间：
2012-05-01
影响因子：
4
通讯作者：
Raghavan, Srikala
中科院分区：
文献类型：
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作者：
Bandyopadhyay, Aditi;Rothschild, Gerson;Raghavan, Srikala
整合素-β 1缺失的角质形成细胞可以通过整合素α v β 6粘附到纤连蛋白上，但形成大的外周局灶性粘附并表现出有缺陷的细胞铺展。在这里，我们报告说，除了α v β 6整合素结合纤连蛋白的亲和力降低，整合素β 6不能有效地结合和招募kindlin-2的粘着斑直接有助于这些表型。Kindlin通过与整联蛋白-β胞质尾直接相互作用来调节整联蛋白，并且角质形成细胞表达Kindlin-1和Kindlin-2。值得注意的是，尽管两种kindlin均定位于野生型细胞中的粘着斑，但仅kindlin-1定位于整合素-β 1-缺失细胞的富含整合素-β 6的粘着斑。用野生型和嵌合整合素构建体拯救这些细胞揭示了kindlin-2募集和细胞扩散之间的相关性。此外，尽管存在kindlin-1，但野生型角质形成细胞中kindlin-2的敲低会损害细胞扩散。我们的数据揭示了两个同源kindlin亚型与两个密切相关的整合素的关联差异的意想不到的功能后果，并表明，尽管它们的相似性，不同的kindlin可能具有独特的功能。
Integrin-beta 1-null keratinocytes can adhere to fibronectin through integrin alpha v beta 6, but form large peripheral focal adhesions and exhibit defective cell spreading. Here we report that, in addition to the reduced avidity of alpha v beta 6 integrin binding to fibronectin, the inability of integrin beta 6 to efficiently bind and recruit kindlin-2 to focal adhesions directly contributes to these phenotypes. Kindlins regulate integrins through direct interactions with the integrin-beta cytoplasmic tail and keratinocytes express kindlin-1 and kindlin-2. Notably, although both kindlins localize to focal adhesions in wild-type cells, only kindlin-1 localizes to the integrin-beta 6-rich adhesions of integrin-beta 1-null cells. Rescue of these cells with wild-type and chimeric integrin constructs revealed a correlation between kindlin-2 recruitment and cell spreading. Furthermore, despite the presence of kindlin-1, knockdown of kindlin-2 in wild-type keratinocytes impaired cell spreading. Our data reveal unexpected functional consequences of differences in the association of two homologous kindlin isoforms with two closely related integrins, and suggest that despite their similarities, different kindlins are likely to have unique functions.