Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Curr Biol. 2009 Sep 15;19(17):1421-8. doi: 10.1016/j.cub.2009.07.018. Epub 2009 Jul 30.
Mechanosensing governs many processes from molecular to organismal levels, including during cytokinesis where it ensures successful and symmetrical cell division. Although many proteins are now known to be force sensitive, myosin motors with their ATPase activity and force-sensitive mechanical steps are well poised to facilitate cellular mechanosensing. For a myosin motor to experience tension, the actin filament must also be anchored.
Here, we find a cooperative relationship between myosin II and the actin crosslinker cortexillin I where both proteins are essential for cellular mechanosensory responses. Although many functions of cortexillin I and myosin II are dispensable for cytokinesis, all are required for full mechanosensing. Our analysis demonstrates that this mechanosensor has three critical elements: the myosin motor where the lever arm acts as a force amplifier, a force-sensitive bipolar thick-filament assembly, and a long-lived actin crosslinker, which anchors the actin filament so that the motor may experience tension. We also demonstrate that a Rac small GTPase inhibits this mechanosensory module during interphase, allowing the module to be primarily active during cytokinesis.
Overall, myosin II and cortexillin I define a cellular-scale mechanosensor that controls cell shape during cytokinesis. This system is exquisitely tuned through the enzymatic properties of the myosin motor, its lever arm length, and bipolar thick-filament assembly dynamics. The system also requires cortexillin I to stably anchor the actin filament so that the myosin motor can experience tension. Through this cross-talk, myosin II and cortexillin I define a cellular-scale mechanosensor that monitors and corrects shape defects, ensuring symmetrical cell division.
机械感知在从分子到生物体的多个层面上控制着许多过程，包括胞质分裂期间的细胞分裂。尽管现在已知许多蛋白质是力敏感的，但具有 ATP 酶活性和力敏感机械步骤的肌球蛋白马达非常适合促进细胞机械感知。为了使肌球蛋白马达感受到张力，肌动蛋白丝也必须被锚定。
在这里，我们发现肌球蛋白 II 和肌动蛋白交联蛋白皮质醇 I 之间存在协同关系，这两种蛋白对于细胞机械感受器的反应都是必不可少的。尽管皮质醇 I 和肌球蛋白 II 的许多功能对于胞质分裂是可有可无的，但它们对于完全的机械感知都是必需的。我们的分析表明，这个机械感受器有三个关键要素：肌球蛋白马达，其中的杠杆臂充当力放大器；力敏感的双极厚丝组装；以及长寿命的肌动蛋白交联蛋白，它锚定肌动蛋白丝，使马达能够感受到张力。我们还证明，Rac 小 GTPase 在间期中抑制这个机械感受器模块，使其在胞质分裂期间主要活跃。
总的来说，肌球蛋白 II 和皮质醇 I 定义了一个细胞尺度的机械感受器，它在胞质分裂期间控制细胞的形状。这个系统通过肌球蛋白马达的酶学特性、其杠杆臂长度和双极厚丝组装动力学得到了精细的调节。该系统还需要皮质醇 I 来稳定地锚定肌动蛋白丝，以使肌球蛋白马达能够感受到张力。通过这种相互作用，肌球蛋白 II 和皮质醇 I 定义了一个细胞尺度的机械感受器，它监测和纠正形状缺陷，确保细胞的对称分裂。
