Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1-and myosin X-dependent manner
Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1-and myosin X-dependent manner
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DOI：
10.1038/sj.emboj.7601599
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发表时间：
2007-03-21
期刊：
影响因子：
11.4
通讯作者：
Nishida, Eisuke
中科院分区：
文献类型：
--
作者：
Toyoshima, Fumiko;Nishida, Eisuke
在极化细胞中，有丝分裂纺锤体的方向受到严格的调控，但在非极化细胞中是否存在调控纺锤体方向的机制尚不清楚。在这里，我们表明，整合素依赖的细胞粘附到基板定向的非极化培养细胞的有丝分裂纺锤体平行于基板平面。纺锤体在铺在纤连蛋白或胶原蛋白上的细胞中正确定向，但在聚-L-赖氨酸上或用RGD肽或抗β 1-整联蛋白抗体处理的细胞中错误定向，表明该机制需要整联蛋白介导的细胞粘附。值得注意的是，这种机制是独立的重力或细胞间粘附，但需要肌动蛋白细胞骨架和星形微管。此外，肌球蛋白X和微管加末端跟踪蛋白EB 1被证明在这一机制中发挥作用，通过重塑肌动蛋白细胞骨架和稳定的星形微管，分别。因此，我们的研究结果揭示了存在一种机制，定向平行于细胞-基质粘附平面的纺锤体，并确定参与这种新机制的关键因素。
The orientation of mitotic spindles is tightly regulated in polarized cells, but it has been unclear whether there is a mechanism regulating spindle orientation in nonpolarized cells. Here we show that integrin-dependent cell adhesion to the substrate orients the mitotic spindle of nonpolarized cultured cells parallel to the substrate plane. The spindle is properly oriented in cells plated on fibronectin or collagen, but misoriented in cells on poly-L-lysine or treated with the RGD peptide or anti-beta 1-integrin antibody, indicating requirement of integrin-mediated cell adhesion for this mechanism. Remarkably, this mechanism is independent of gravitation or cell-cell adhesion, but requires actin cytoskeleton and astral microtubules. Furthermore, myosin X and the microtubule plus-end-tracking protein EB1 are shown to play a role in this mechanism through remodeling of actin cytoskeleton and stabilization of astral microtubules, respectively. Our results thus uncover the existence of a mechanism that orients the spindle parallel to the cell-substrate adhesion plane, and identify crucial factors involved in this novel mechanism.