A mechanism with severing near barbed ends and annealing explains structure and dynamics of dendritic actin networks
A mechanism with severing near barbed ends and annealing explains structure and dynamics of dendritic actin networks
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DOI：
10.1101/2021.03.31.437985
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发表时间：
2021-04
期刊：
影响因子：
7.7
通讯作者：
D. Holz;Aaron R. Hall;Eiji Usukura;S. Yamashiro;N. Watanabe;Dimitrios Vavylonis
中科院分区：
文献类型：
--
作者：
D. Holz;Aaron R. Hall;Eiji Usukura;S. Yamashiro;N. Watanabe;Dimitrios Vavylonis
单分子成像显示，在片状脂虫中，肌动蛋白的一部分在进入树突细丝网络后几秒钟内解体，这表明在带刺末端附近经常发生不稳定。为了研究网络重构背后的机制，我们建立了一个包含聚合、解聚、支化、封顶、解帽、切断、齐聚物扩散、退火和去支化的随机模型。我们发现，如果寡聚体片段以与体外测量相当的速率常数重新退火到自由端，那么在带刺末端附近增强的丝状断丝可以解释单分子肌动蛋白的寿命分布。相同的机制导致肌动蛋白网络与测量的细丝、末端和分支浓度一致。这些网络经历了结构重塑，导致+/-35°取向的细丝远离前沿。亚秒分辨率的肌动蛋白斑点寿命成像验证了新组装的肌动蛋白的频繁分解。因此，我们提出了一种统一的机制，该机制适合一套不同的基本片状脂血症现象学。
Single molecule imaging has shown that part of actin disassembles within a few seconds after incorporation into the dendritic filament network in lamellipodia, suggestive of frequent destabilization near barbed ends. To investigate the mechanisms behind network remodeling, we created a stochastic model with polymerization, depolymerization, branching, capping, uncapping, severing, oligomer diffusion, annealing, and debranching. We find that filament severing, enhanced near barbed ends, can explain the single molecule actin lifetime distribution, if oligomer fragments reanneal to free ends with rate constants comparable to in vitro measurements. The same mechanism leads to actin networks consistent with measured filament, end, and branch concentrations. These networks undergo structural remodeling, leading to longer filaments away from the leading edge, at the +/- 35° orientation pattern. Imaging of actin speckle lifetimes at sub-second resolution verifies frequent disassembly of newly-assembled actin. We thus propose a unified mechanism that fits a diverse set of basic lamellipodia phenomenology.