标题： 核形成反馈可以驱动神经突中偏斜微管极性的建立和维持 显示英文标题

标题： Nucleation feedback can drive establishment and maintenance of biased microtubule polarity in neurites

摘要： 微管细胞骨架由动态的、极性的丝状结构组成，有助于细胞内的运输。 极性的微管阵列对于长细胞（如神经元）中的货物运输至关重要。 微管也经历动态不稳定性，其中丝状物的正端和负端在生长和缩短阶段之间切换，导致频繁的微管更新。 尽管微管经常完全解聚并形成新的丝状物，但已观察到微管阵列在整个细胞生命周期中保持其偏倚方向，并且在应对损伤时重新排列其极性作为适应性反应。 受神经突起中细胞骨架组织的启发，我们提出了一种空间显式的随机模型来研究微管阵列，并探讨新丝状物的成核如何在简单的线性域中产生偏倚极性。 使用连续时间马尔可夫链模型对微管生长动力学进行建模和参数化，我们模拟并验证了两种实验验证的成核机制：成核反馈，其中丝状物的生长方向取决于现有的微管内容，以及检查点机制，其中在与大多数方向相反的方向上成核的微管会经历频繁的灾难。 当将这些经过验证的机制纳入空间模型时，我们发现成核反馈足以在不同长度的神经突起中建立偏倚极性，并且偏倚极性的出现和维持在随机波动下相对稳定。 这项工作提供了一个研究微管成核与极性之间关系的框架，并可能扩展以提供关于其他生物环境中极性丝状物阵列形成机制的见解。 显示英文摘要

摘要： The microtubule cytoskeleton is comprised of dynamic, polarized filaments that facilitate transport within the cell. Polarized microtubule arrays are key to facilitating cargo transport in long cells such as neurons. Microtubules also undergo dynamic instability, where the plus and minus ends of the filaments switch between growth and shrinking phases, leading to frequent microtubule turnover. Although microtubules often completely disassemble and new filaments nucleate, microtubule arrays have been observed to both maintain their biased orientation throughout the cell lifetime and to rearrange their polarity as an adaptive response to injury. Motivated by cytoskeleton organization in neurites, we propose a spatially-explicit stochastic model of microtubule arrays and investigate how nucleation of new filaments could generate biased polarity in a simple linear domain. Using a continuous-time Markov chain model of microtubule growth dynamics, we model and parameterize two experimentally-validated nucleation mechanisms: nucleation feedback, where the direction of filament growth depends on existing microtubule content, and a checkpoint mechanism, where microtubules that nucleate in a direction opposite to the majority experience frequent catastrophe. When incorporating these validated mechanisms into the spatial model, we find that nucleation feedback is sufficient to establish biased polarity in neurites of different lengths, and that the emergence and maintenance of biased polarity is relatively stable in spite of stochastic fluctuations. This work provides a framework to study the relationship between microtubule nucleation and polarity, and could extend to give insights into mechanisms that drive the formation of polarized filament arrays in other biological settings.