The Motion of An Inv Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization
The Motion of An Inv Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization
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反节点纤毛的运动：揭示动力蛋白驱动的纤毛运动与微管错误定位的现实模型
DOI：
10.1159/000496038
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
D. Chen
中科院分区：
文献类型：
--
作者：
Y. Yu;K. Shinohara;H. Xu;Z. Li;T. Nishida;H. Hamada;X. Xu;J. Zhou;D. Shao;X. Li;D. Chen
背景/目的：在胚胎发生过程中，在腹侧结旋转的节毛在左右不对称的形成中起重要作用；然而，非突变纤毛呈现异常运动并引起侧边缺陷。它们的运动机制受动力蛋白激活和微管排列的调节，目前还不完全清楚。本研究分析了inv突变体异常超微结构中动力蛋白触发的纤毛运动，旨在定量评价微管定位错误对纤毛运动的影响。方法：基于超高压电子显微镜生成的层析成像数据集，建立具有超微结构的非突变体纤毛的真实三维模型。在该数学模型中，轴突动力的时变激活通过对点载荷和嵌入在相邻微管双偶之间的动力安装位置来模拟。利用有限元法和可变形网格，研究了不同动力蛋白激活假说下突变体纤毛的运动特性，并与实验观察结果进行了比较。结果：对于非突变体，在部分激活情况下，基于距离控制模式的纤毛运动模拟与观察结果基本一致；微管的缩短导致纤毛的运动幅度减小，而微管的错位角度影响纤毛的运动模式，在纤毛运动过程中，微管在突变体纤毛中发生摆动和扭曲。结论：更一般地说，本研究表明动力蛋白接合对轴突的细微几何变化很敏感，因此，这种几何变化极大地影响了形成良好的纤毛旋转的完整性。
Background/Aims: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. Methods: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. Results: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. Conclusion: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation.
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DOI：
10.1016/s0021-9258(17)36840-0
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Pascal Venier;Anthony;-C.;MaggsS;M. Carlier;D. Pantaloni
通讯作者：
Pascal Venier;Anthony;-C.;MaggsS;M. Carlier;D. Pantaloni
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影响因子：
3
作者：
Yan T;Feng Y;Liu T;Wang L;Mu N;Dong X;Liu Z;Qin T;Tang X;Zhao L
通讯作者：
Zhao L
DOI：
--
发表时间：
2016
期刊：
--
影响因子：
--
作者：
T. Nakanishi;Markwald Rr;Baldwin Hs;B. Keller;D. Srivastava;H. Yamagishi
通讯作者：
T. Nakanishi;Markwald Rr;Baldwin Hs;B. Keller;D. Srivastava;H. Yamagishi
DOI：
10.1098/rspa.2009.0018
发表时间：
2009-08
期刊：
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
影响因子：
--
作者：
David J. Smith;E. Gaffney;J. Blake
通讯作者：
David J. Smith;E. Gaffney;J. Blake
影响因子：
11.8
作者：
K. Shinohara;Duanduan Chen;T. Nishida;K. Misaki;S. Yonemura;H. Hamada
通讯作者：
K. Shinohara;Duanduan Chen;T. Nishida;K. Misaki;S. Yonemura;H. Hamada