Disruption of focal adhesions by integrin cytoplasmic domain-associated protein-1α
Disruption of focal adhesions by integrin cytoplasmic domain-associated protein-1α
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DOI：
10.1074/jbc.m211258200
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发表时间：
2003-02-21
影响因子：
4.8
通讯作者：
Block, MR
中科院分区：
文献类型：
--
作者：
Bouvard, D;Vignoud, L;Block, MR
整合素的亲和力和聚集性的调节在细胞粘附和迁移的控制中起着关键作用。蛋白质ICAP-1 α（整合素胞质结构域相关蛋白-1 α）与β（1A）整合素的胞质结构域结合并控制纤连蛋白上的细胞铺展。在这里，我们证明，尽管其与β（1A）整合素相互作用的能力，ICAP-1 α是不招募局灶性粘连，而它是共定位与整合素在皱褶边缘的细胞。ICAP-1 α诱导局灶性粘连的快速破坏，这可能是由于ICAP-1 α抑制β（1A）整合素与talin结合的能力，这对这些结构的组装至关重要。在不结合ICAP的β（1D）整联蛋白中未观察到ICAP-1 α介导的β（1A）整联蛋白分散。这有力地表明，ICAP-1 α的作用依赖于ICAP-1 α和β 1链胞质结构域之间的直接相互作用。总之，这些结果表明ICAP-1 α通过作为β 1整合素亲合力的负调节剂在细胞粘附中起关键作用。
Regulation of integrin affinity and clustering plays a key role in the control of cell adhesion and migration. The protein ICAP-1alpha (integrin cytoplasmic domain-associated protein-1alpha) binds to the cytoplasmic domain of the beta(1A) integrin and controls cell spreading on fibronectin. Here, we demonstrate that, despite its ability to interact with beta(1A) integrin, ICAP-1alpha is not recruited in focal adhesions, whereas it is colocalized with the integrin at the ruffling edges of the cells. ICAP-1alpha induced a rapid disruption of focal adhesions, which may result from the ability of ICAP-1alpha to inhibit the association of beta(1A) integrin with talin, which is crucial for the assembly of these structures. ICAP-1alpha-mediated dispersion of beta(1A) integrins is not observed with beta(1D) integrins that do not bind ICAP. This strongly suggests that ICAP-1alpha action depends on a direct interaction between ICAP-1alpha and the cytoplasmic domain of the beta(1) chains. Altogether, these results suggest that ICAP-1alpha plays a key role in cell adhesion by acting as a negative regulator of beta(1) integrin avidity.