A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting.
A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting.
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DOI：
10.1038/ncomms7135
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发表时间：
2015-01-22
影响因子：
16.6
通讯作者：
Humphries MJ
中科院分区：
文献类型：
--
作者：
Byron A;Askari JA;Humphries JD;Jacquemet G;Koper EJ;Warwood S;Choi CK;Stroud MJ;Chen CS;Knight D;Humphries MJ
整合素的激活受受体构象的变构调节，使细胞能够对细胞外微环境的化学、机械和拓扑特征做出反应。然而，对于激活状态如何将整合素近端区域的分子组成转化为功能读出缺乏全球观点。在这里，我们使用构象特异的单抗，分离整合素激活状态依赖的复合体，并用质谱仪对其进行表征。定量比较结合了网络、聚类、路径和图像分析，定义了以构象特定方式丰富的多个功能蛋白质模块。值得注意的是，活性整合素复合体对与基于微管的功能相关的蛋白质具有特定的富集性。微管在微图案化表面的可视化和活细胞成像表明，活性整合素建立了稳定细胞外围微管的环境。这些数据为询问将整合素激活与黏附信号联系在一起的全球分子连接提供了资源。整合素被许多细胞外信号激活，并通过组装不同的信号复合体来做出反应。拜伦等人。使用激活状态特异性抗体来描述这些复合体的蛋白质特征，并提供对整合素依赖的微管稳定的洞察。
Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling. Integrins are activated by many extracellular cues and respond by assembling diverse signalling complexes. Byron et al. use activation state-specific antibodies to proteomically characterize these complexes, and provide insight into integrin-dependent microtubule stabilization.
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影响因子：
64.5
作者：
Fukata, M;Watanabe, T;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
64.8
作者：
Chicurel, ME;Singer, RH;Ingber, DE
通讯作者：
Ingber, DE
影响因子：
21.3
作者：
Balasubramanian, Nagaraj;Scott, David W.;Schwartz, Martin Alexander
通讯作者：
Schwartz, Martin Alexander
影响因子：
19
作者：
Guilluy C;Garcia-Mata R;Burridge K
通讯作者：
Burridge K
DOI：
10.1083/jcb.200907174
发表时间：
2010-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Askari JA;Tynan CJ;Webb SE;Martin-Fernandez ML;Ballestrem C;Humphries MJ
通讯作者：
Humphries MJ