Mechanochemical Crosstalk Produces Cell-Intrinsic Patterning of the Cortex to Orient the Mitotic Spindle.
Mechanochemical Crosstalk Produces Cell-Intrinsic Patterning of the Cortex to Orient the Mitotic Spindle.
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DOI：
10.1016/j.cub.2020.06.098
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发表时间：
2020-09-21
期刊：
影响因子：
--
通讯作者：
Baum B
中科院分区：
文献类型：
--
作者：
Dimitracopoulos A;Srivastava P;Chaigne A;Win Z;Shlomovitz R;Lancaster OM;Le Berre M;Piel M;Franze K;Salbreux G;Baum B
尽管在进入有丝分裂过程中纺锤体会变圆，但发育中的动物细胞仍能使其有丝分裂纺锤体沿着其间期细胞轴定向，从而建立起细胞分裂轴。这以前被归因于分子记忆，更具体地说，归因于有丝分裂中粘附和收缩纤维的维持，这被认为是对皮质Gαi、LGN和核有丝分裂器蛋白（NuMA）进行模式化的局部线索。然后，这种皮质机制招募并激活动力蛋白马达，动力蛋白马达拉动星形微管以定位有丝分裂纺锤体。在这里，我们揭示了一个动态的双向串扰之间的主轴和皮质运动复合体，取决于RAN-鸟苷三磷酸（GTP）信号，这是足以驱动连续的单极主轴运动独立于粘合剂线索在扁平的人类细胞培养。在以前工作的基础上，我们实现了一个物理模型的系统，概括观察到的纺锤体皮层的相互作用。引人注目的是，当这个模型被用来研究进入有丝分裂的细胞中的纺锤体动力学时，基于染色质的信号被发现优先清除来自短细胞轴的力发生器，因此，拉动星形微管的皮质马达将双极纺锤体与间期长细胞轴对齐，而不需要固定的线索或间期形状的物理记忆。因此，我们的分析表明，染色质在有丝分裂变圆过程中形成皮质图案的能力足以将间期形状转化为可以由纺锤体读取的皮质图案，纺锤体然后引导细胞分裂的轴。单极纺锤体在扁平有丝分裂细胞中进行持续的追逐和奔跑运动纺锤体运动依赖于微管、LGN和Ran-GTP通路一个机械化学计算模型概括了单极纺锤体运动该模型显示了纺锤体在有丝分裂圆化过程中如何沿沿着长细胞轴定向Dimitracopoulos et al.显示皮质和纺锤体之间的双向反馈如何驱动培养中有丝分裂细胞中不稳定的纺锤体运动，并显示这种动态系统如何能够定向有丝分裂纺锤体，使其与间期长细胞轴对齐，即使在没有外部线索的情况下。
Proliferating animal cells are able to orient their mitotic spindles along their interphase cell axis, setting up the axis of cell division, despite rounding up as they enter mitosis. This has previously been attributed to molecular memory and, more specifically, to the maintenance of adhesions and retraction fibers in mitosis, which are thought to act as local cues that pattern cortical Gαi, LGN, and nuclear mitotic apparatus protein (NuMA). This cortical machinery then recruits and activates Dynein motors, which pull on astral microtubules to position the mitotic spindle. Here, we reveal a dynamic two-way crosstalk between the spindle and cortical motor complexes that depends on a Ran-guanosine triphosphate (GTP) signal, which is sufficient to drive continuous monopolar spindle motion independently of adhesive cues in flattened human cells in culture. Building on previous work, we implemented a physical model of the system that recapitulates the observed spindle-cortex interactions. Strikingly, when this model was used to study spindle dynamics in cells entering mitosis, the chromatin-based signal was found to preferentially clear force generators from the short cell axis, so that cortical motors pulling on astral microtubules align bipolar spindles with the interphase long cell axis, without requiring a fixed cue or a physical memory of interphase shape. Thus, our analysis shows that the ability of chromatin to pattern the cortex during the process of mitotic rounding is sufficient to translate interphase shape into a cortical pattern that can be read by the spindle, which then guides the axis of cell division. Monopolar spindles undergo persistent chase and run movements in flat mitotic cells Spindle movements depend on microtubules, LGN, and the Ran-GTP pathway A mechanochemical computational model recapitulates monopolar spindle movements The model shows how spindles orient along the long cell axis during mitotic rounding Dimitracopoulos et al. show how two-way feedback between the cortex and the spindle drives unstable spindle movements in mitotic cells in culture and show how this dynamic system is able to orient the mitotic spindle so that it aligns with the interphase long cell axis, even in the absence of external cues.
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DOI：
10.1083/jcb.201401049
发表时间：
2014-06-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Machicoane M;de Frutos CA;Fink J;Rocancourt M;Lombardi Y;Garel S;Piel M;Echard A
通讯作者：
Echard A
影响因子：
2.5
作者：
Le Berre, Mael;Aubertin, Johannes;Piel, Matthieu
通讯作者：
Piel, Matthieu
影响因子：
64.5
作者：
Merdes, A;Ramyar, K;Cleveland, DW
通讯作者：
Cleveland, DW
影响因子：
64.5
作者：
Minc N;Burgess D;Chang F
通讯作者：
Chang F
影响因子：
16.6
作者：
Cadart C;Monnier S;Grilli J;Sáez PJ;Srivastava N;Attia R;Terriac E;Baum B;Cosentino-Lagomarsino M;Piel M
通讯作者：
Piel M