Minimal Mechanisms of Microtubule Length Regulation in Living Cells
Minimal Mechanisms of Microtubule Length Regulation in Living Cells
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DOI：
10.1007/s11538-024-01279-z
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发表时间：
2024-05-01
影响因子：
3.5
通讯作者：
Mckinley，Scott A.
中科院分区：
文献类型：
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作者：
Nelson，Anna C.;Rolls，Melissa M.;Mckinley，Scott A.
微管细胞骨架负责神经元中 mRNA、蛋白质和细胞器的持续、长距离细胞内运输。神经元微管必须足够稳定以确保可靠的运输，但它们也会经历动态不稳定，因为它们的正负端不断在生长和收缩之间切换。这个过程允许细胞骨架的持续重建和损伤情况下的灵活性。受果蝇神经元微管行为的体内实验数据的启发，我们提出了树突微管动力学的数学模型，重点是了解微管长度、速度和状态持续时间分布。我们发现，现实动力学需要对微管生长阶段进行限制，但限制机制的类型会导致对可能的实验扰动产生不同的反应。因此，我们提出并研究了两个最小复杂的长度限制因素：由于资源（微管蛋白）限制而导致的限制和由于大长度微管的灾难而导致的限制。我们将详细随机模型的模拟与平均场常微分方程模型的稳态分析相结合，以绘制出定性不同的参数范围。这为预测不同实验环境中微管动力学、微管蛋白分配以及微管内微管蛋白周转率的变化提供了基础。
The microtubule cytoskeleton is responsible for sustained, long-range intracellular transport of mRNAs, proteins, and organelles in neurons. Neuronal microtubules must be stable enough to ensure reliable transport, but they also undergo dynamic instability, as their plus and minus ends continuously switch between growth and shrinking. This process allows for continuous rebuilding of the cytoskeleton and for flexibility in injury settings. Motivated by in vivo experimental data on microtubule behavior inDrosophilaneurons, we propose a mathematical model of dendritic microtubule dynamics, with a focus on understanding microtubule length, velocity, and state-duration distributions. We find that limitations on microtubule growth phases are needed for realistic dynamics, but the type of limiting mechanism leads to qualitatively different responses to plausible experimental perturbations. We therefore propose and investigate two minimally-complex length-limiting factors: limitation due to resource (tubulin) constraints and limitation due to catastrophe of large-length microtubules. We combine simulations of a detailed stochastic model with steady-state analysis of a mean-field ordinary differential equations model to map out qualitatively distinct parameter regimes. This provides a basis for predicting changes in microtubule dynamics, tubulin allocation, and the turnover rate of tubulin within microtubules in different experimental environments.