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A mechanosensory system governs myosin II accumulation in dividing cells

机译:机械感觉系统控制分裂细胞中肌球蛋白II的积累

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摘要

The mitotic spindle is generally considered the initiator of furrow ingression. However, recent studies suggest that furrows can form without spindles, particularly during asymmetric cell division. In Dictyostelium, the mechanoenzyme myosin II and the actin cross-linker cortexillin I form a mechanosensor that responds to mechanical stress, which could account for spindle-independent contractile protein recruitment. Here we show that the regulatory and contractility network composed of myosin II, cortexillin I, IQGAP2, kinesin-6 (kif12), and inner centromeric protein (INCENP) is a mechanical stress–responsive system. Myosin II and cortexillin I form the core mechanosensor, and mechanotransduction is mediated by IQGAP2 to kif12 and INCENP. In addition, IQGAP2 is antagonized by IQGAP1 to modulate the mechanoresponsiveness of the system, suggesting a possible mechanism for discriminating between mechanical and biochemical inputs. Furthermore, IQGAP2 is important for maintaining spindle morphology and kif12 and myosin II cleavage furrow recruitment. Cortexillin II is not directly involved in myosin II mechanosensitive accumulation, but without cortexillin I, cortexillin II's role in membrane–cortex attachment is revealed. Finally, the mitotic spindle is dispensable for the system. Overall, this mechanosensory system is structured like a control system characterized by mechanochemical feedback loops that regulate myosin II localization at sites of mechanical stress and the cleavage furrow.
机译:通常认为有丝分裂纺锤体是沟进入的发起者。但是,最近的研究表明,犁沟可以在没有纺锤体的情况下形成,特别是在不对称细胞分裂过程中。在盘基网柄菌中,机械酶肌球蛋白II和肌动蛋白交联剂Cortexillin I形成了一种机械传感器,该传感器响应机械应力,这可能是与纺锤体无关的收缩蛋白募集的原因。在这里,我们表明由肌球蛋白II,皮质醇I,IQGAP2,驱动蛋白6(kif12)和内部着丝粒蛋白(INCENP)组成的调节和收缩网络是机械应激反应系统。肌球蛋白II和皮质激素I形成了核心的机械传感器,机械传导是由IQGAP2介导到kif12和INCENP。此外,IQGAP1拮抗了IQGAP2,以调节系统的机械响应性,提示了区分机械输入和生化输入的可能机制。此外,IQGAP2对于维持纺锤体形态以及kif12和肌球蛋白II切割沟的募集非常重要。皮质醇II不直接参与肌球蛋白II的机械敏感性积累,但是如果没有皮质醇I,则皮质醇II在膜-皮质附着中的作用被揭示。最后,有丝分裂纺锤体对于该系统是必不可少的。总体而言,该机械感觉系统的结构类似于控制系统,其特征在于机械化学反馈回路可调节肌球蛋白II在机械应力和裂沟处的定位。

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