Selective modulation of integrin-mediated cell migration by distinct ADAM family members
Selective modulation of integrin-mediated cell migration by distinct ADAM family members
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DOI：
10.1091/mbc.e05-03-0258
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
White, JM
中科院分区：
文献类型：
--
作者：
Huang, J;Bridges, LC;White, JM
解整合素和金属蛋白酶（ADAM）家族成员参与许多生物过程。尽管人们认识到重组ADAM去整合素结构域可以与整合素相互作用，但对细胞背景下的ADAM-整合素相互作用知之甚少。在这里，我们测试了亚当斯是否可以选择性地调节整合素介导的细胞迁移。在表达确定的整合素（α 4 β 1、α 5 β 1或两者）的中国仓鼠卵巢细胞中表达亚当斯，并研究了全长纤连蛋白或其α 4 β 1或α 5 β 1结合片段上的细胞迁移。我们发现，亚当斯抑制整合素介导的细胞迁移的模式所决定的整合素结合档案的分离的去整合素域。ADAM 12抑制由α 4 β 1介导的细胞迁移，但不抑制α 5 β 1整合素。ADAM 17具有相反的作用;它抑制α 5 β 1介导的细胞迁移，但不抑制α 4 β 1介导的细胞迁移。ADAM 19和ADAM 33抑制由α 4 β 1和α 5 β 1整联蛋白介导的迁移。ADAM 12去整合素环中的点突变部分降低了ADAM 12对纤维连接蛋白α 4 β 1结合片段细胞迁移的抑制作用，而阻断金属蛋白酶活性的突变则没有影响。我们的研究结果表明，不同的亚当斯可以调节特定的整合素介导的细胞迁移的模式决定，至少部分，由他们的去整合素结构域。
A disintegrin and a metalloprotease (ADAM) family members have been implicated in many biological processes. Although it is recognized that recombinant ADAM disintegrin domains can interact with integrins, little is known about ADAM-integrin interactions in cellular context. Here, we tested whether ADAMs can selectively regulate integrin-mediated cell migration. ADAMs were expressed in Chinese hamster ovary cells that express defined integrins (alpha 4 beta 1, alpha 5 beta 1, or both), and cell migration on full-length fibronectin or on its alpha 4 beta 1 or alpha 5 beta 1 binding fragments was studied. We found that ADAMs inhibit integrin-mediated cell migration in patterns dictated by the integrin binding profiles of their isolated disintegrin domains. ADAM12 inhibited cell migration mediated by the alpha 4 beta 1 but not the alpha 5 beta 1 integrin. ADAM17 had the reciprocal effect; it inhibited alpha 5 beta 1- but not alpha 4 beta 1-mediated cell migration. ADAM19 and ADAM33 inhibited migration mediated by both alpha 4 beta 1 and alpha 5 beta 1 integrins. A point mutation in the ADAM12 disintegrin loop partially reduced the inhibitory effect of ADAM12 on cell migration on the alpha 4 beta 1 binding fragment of fibronectin, whereas mutations that block metalloprotease activity had no effect. Our results indicate that distinct ADAMs can modulate cell migration mediated by specific integrins in a pattern dictated, at least in part, by their disintegrin domains.