A ligand-independent integrin β1 mechanosensory complex guides spindle orientation.
A ligand-independent integrin β1 mechanosensory complex guides spindle orientation.
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DOI：
10.1038/ncomms10899
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发表时间：
2016-03-08
影响因子：
16.6
通讯作者：
Skourides PA
中科院分区：
文献类型：
--
作者：
Petridou NI;Skourides PA
纺锤体方向的控制是胚胎发育、形态发生和组织稳态的基本过程，而缺陷与肿瘤发生和其他疾病有关。力感是决定分裂方向的机制之一。在这里，我们表明，整合素β1在这一过程中起着关键作用，成为激活在细胞皮质的侧区在配体非依赖性的方式。这种激活是力依赖性和极性的，与纺锤体捕获位点相关。抑制整合素β1在皮质上的活化和破坏其不对称分布导致纺锤体定向错误，即使细胞粘附是β1非依赖性的。对下游靶点的研究表明，皮质机械感觉复合体在活性β1上形成，并调节纺锤体方向，而与细胞环境无关。我们认为，配体非依赖性整合素β1激活是一种保守的机制，允许细胞对外部刺激作出反应。 在细胞分裂期间，有丝分裂纺锤体的方向对施加在细胞皮层上的力敏感。在这里，Petridou和Skourides表明，这些线索是由建立在力激活整合素β1上的机械感觉复合体感受到的，而不依赖于配体结合。
Control of spindle orientation is a fundamental process for embryonic development, morphogenesis and tissue homeostasis, while defects are associated with tumorigenesis and other diseases. Force sensing is one of the mechanisms through which division orientation is determined. Here we show that integrin β1 plays a critical role in this process, becoming activated at the lateral regions of the cell cortex in a ligand-independent manner. This activation is force dependent and polar, correlating with the spindle capture sites. Inhibition of integrin β1 activation on the cortex and disruption of its asymmetric distribution leads to spindle misorientation, even when cell adhesion is β1 independent. Examining downstream targets reveals that a cortical mechanosensory complex forms on active β1, and regulates spindle orientation irrespective of cell context. We propose that ligand-independent integrin β1 activation is a conserved mechanism that allows cell responses to external stimuli. During cell division, the orientation of the mitotic spindle is sensitive to forces exerted on the cell cortex. Here Petridou and Skourides show that such cues are sensed by a mechanosensory complex established on force activated integrin β1 independent of ligand binding.