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Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers.
Cytoskeleton ( IF 2.9 ) Pub Date : 2019-12-13 , DOI: 10.1002/cm.21574
Manuel Lera-Ramirez 1 , François J Nédélec 2
Affiliation  

Antiparallel microtubule bundles are essential structural elements of many cytoskeletal structures, for instance, the mitotic spindle. Sliding of microtubules relative to each other can lead to an overall elongation of the bundle. However, such sliding must be accompanied by microtubule growth, to maintain the overlap, which is a landmark of anaphase. Diffusive crosslinkers of the Ase1/PRC1/MAP65 family are able to form stable overlaps in combination with kinesin‐14 motors. This process is thought to arise through a balance of forces between motors and crosslinkers, the latter effectively producing an entropic pressure. We provide a continuous theory to explain the formation of stable overlaps, in which steric effects caused by the finite number of binding sites available on the microtubule lattice play a leading role. We confirmed the validity of this approach using discrete stochastic simulations performed with the Open Source simulation engine Cytosim. From the densities of motors and crosslinkers, their diffusion rates, and the velocities of motors, the theory predicts the sliding speed of microtubules and explains the force production and breaking effect of crosslinkers and motors containing diffusible microtubule‐binding domains. Finally, we discuss a mechanism by which sliding and microtubule growth can be coordinated without the need for fine‐tuning the parameters of the system, in line with the known robustness of mitosis.

中文翻译:

通过马达和可扩散交联剂实现的反平行微管重叠稳定理论。

反平行微管束是许多细胞骨架结构(例如,有丝分裂纺锤体)的必不可少的结构元素。微管相对于彼此的滑动会导致束的整体伸长。然而,这种滑动必须伴随着微管生长,以保持重叠,这是后期的标志。与驱动蛋白14电机组合使用时,Ase1 / PRC1 / MAP65系列的扩散性交联剂能够形成稳定的重叠。人们认为该过程是通过电动机和交联剂之间的力平衡而产生的,交联剂有效地产生了熵压。我们提供了一个连续的理论来解释稳定重叠的形成,其中由微管晶格上可用的有限数量的结合位点引起的空间效应起着主导作用。我们使用由开放源代码仿真引擎Cytosim执行的离散随机仿真证实了该方法的有效性。从马达和交联剂的密度,它们的扩散速率和马达的速度,该理论预测了微管的滑动速度,并解释了包含可扩散微管结合域的交联剂和马达的力产生和破坏作用。最后,我们讨论了一种机制,根据已知的有丝分裂的稳健性,可以通过该机制协调滑动和微管的生长,而无需微调系统参数。该理论预测了微管的滑动速度,并解释了包含可扩散微管结合域的交联剂和马达的力产生和破坏作用。最后,我们讨论了一种机制,根据已知的有丝分裂的稳健性,可以通过该机制协调滑动和微管的生长,而无需微调系统参数。该理论预测了微管的滑动速度,并解释了包含可扩散微管结合域的交联剂和马达的力产生和破坏作用。最后,我们讨论了一种机制,根据已知的有丝分裂的稳健性,可以通过该机制协调滑动和微管的生长,而无需微调系统参数。
更新日期:2019-12-13
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