Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions.
Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions.
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DOI：
10.1083/jcb.201707075
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发表时间：
2018-06-04
期刊：
影响因子：
--
通讯作者：
Strömblad S
中科院分区：
文献类型：
--
作者：
Spiess M;Hernandez-Varas P;Oddone A;Olofsson H;Blom H;Waithe D;Lock JG;Lakadamyali M;Strömblad S
通过两种超分辨率显微镜技术，STED和STORM，Spiess等人可视化了局灶性粘连中整合素的组织，并显示活性和非活性β1整合素在粘连中组装成不同的纳米簇，表明存在局部协调整合素活性的新机制。整合素是细胞-基质粘附复合物如粘着斑（focal adhesion，FA）的核心成分，并且在生理学和疾病中起关键作用。整合素在活性和非活性构象之间波动，但活性状态是否影响FA内整合素的空间组织仍不清楚。在这项研究中，我们解决了这个问题，并询问整合素活性是否可以独立调节每个整合素分子或通过局部协调机制。我们使用两种不同的超分辨率显微镜技术，随机光学重建显微镜（STORM）和受激发射损耗显微镜（STED），以可视化活性与非活性β1整合素。我们首先揭示了整合素组织的空间层次结构与整合素分子排列在纳米簇，对齐，形成线性的子结构，反过来建立脂肪酸。值得注意的是，在FA内，活性和非活性β1整联蛋白分离成不同的纳米簇，其中活性整联蛋白纳米簇更有组织。这种意想不到的分离表明纳米簇内整合素活性的同步，这意味着整合素活性调节的协调机制的存在。
Through two superresolution microscopy techniques, STED and STORM, Spiess et al. visualize the organization of integrins in focal adhesions and show that active and inactive β1 integrins assemble into distinct nanoclusters within adhesions, suggesting the existence of a novel mechanism that locally coordinates integrin activity. Integrins are the core constituents of cell–matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs has remained unclear. In this study, we address this question and also ask whether integrin activity may be regulated either independently for each integrin molecule or through locally coordinated mechanisms. We used two distinct superresolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion microscopy (STED), to visualize active versus inactive β1 integrins. We first reveal a spatial hierarchy of integrin organization with integrin molecules arranged in nanoclusters, which align to form linear substructures that in turn build FAs. Remarkably, within FAs, active and inactive β1 integrins segregate into distinct nanoclusters, with active integrin nanoclusters being more organized. This unexpected segregation indicates synchronization of integrin activities within nanoclusters, implying the existence of a coordinate mechanism of integrin activity regulation.
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