Microtubule dynamics: Caps, catastrophes, and coupled hydrolysis
Microtubule dynamics: Caps, catastrophes, and coupled hydrolysis
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DOI：
10.1103/physreve.54.5538
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发表时间：
1996-11-01
影响因子：
2.4
通讯作者：
Leibler, S
中科院分区：
文献类型：
--
作者：
Flyvbjerg, H;Holy, TE;Leibler, S
为三磷酸鸟苷 (GTP) 帽的动力学制定了一个有效的理论，据信该帽可以稳定生长的微管。该理论提供了上限动态的“粗粒度”描述。 “微观”细节，例如微管晶格结构及其单个微管蛋白二聚体的命运，被忽视了。在此帽模型中，假定 GTP 水解是随机的且与微管生长无关。假定帽内部的 GTP 和其与微管水解部分边界处的 GTP 具有不同的水解速率。得出与可用实验数据相关的期望值和概率分布。发现帽很短，并且发现微管末端的总水解速率与生长动态耦合。所谓的灾难率是微管生长稀有度的简单函数，并且符合实验数据。预计在高增长率下，会出现罕见的恒定非零灾难，微管两端相同。稀释引起的灾难的延迟时间是随机的，具有适合实验分布的简单分布，并且与实验分布一样，不依赖于稀释前微管生长的速率。在旨在测量该GTP含量的实验中所创建的环境下，发现了微管的GTP含量并确定了其水解的罕见性。结论是，本次实验未注册任何GTP内容与模型一致。从之前的实验结果中提取了帽模型的参数后，最近关于可以稳定微管的最小帽尺寸的实验结果表明，与帽模型预测的结果一致。因此，这里提出的有效理论和上限模型为几个明显矛盾的实验数据提供了统一的描述。根据模型讨论了不同浓度的镁离子和微管相关蛋白的灾难率的实验结果。提出了可行的实验，可以为模型提供决定性的检验，并以更高的精度确定其三个参数。
An effective theory is formulated for the dynamics of the guanosine triphosphate (GTP) cap believed to stabilize growing microtubules. The theory provides a ''coarse-grained'' description of the cap's dynamics. ''Microscopic'' details, such as the microtubule lattice structure and the fate of its individual tubulin dimers, an ignored. In this cap model, GTP hydrolysis is assumed to be stochastic and uncoupled to microtubule growth. Different rates of hydrolysis are assumed for GTP in the cap's interior and for GTP at its boundary with hydrolyzed parts of the microtubule. Expectation values and probability distributions relating to available experimental data are derived. Caps are found to be short and the total rate of hydrolysis at a microtubule end is found to be dynamically coupled to growth. The so-called catastrophe rate is a simple function of the microtubule growth rare and fits experimental data. A constant nonzero catastrophe rare, identical for both microtubule ends, is predicted at large growth rates. The delay time for dilution-induced catastrophes is stochastic with a simple distribution that fits the experimental one and, like the experimental one, does not depend on the rate of microtubule growth before dilution. The GTP content of microtubules is found and its rare of hydrolysis is determined under the circumstances created in an experiment designed to measure this GTP content. It is concluded that this experiment's failure to register any GTP content is consistent with the model. A recent experimental result for the size of the minimal cap that can stabilize a microtubule is shown to agree with the result predicted by the cap model, after its parameters have been extracted from previous experimental results. Thus the effective theory and cap model presented here provide a unified description of several apparently contradictory experimental data. Experimental results for the catastrophe rate at different concentrations of magnesium ions and of microtubule associated proteins are discussed in terms of the model. Feasible experiments are suggested that can provide decisive tests of the model and determine its three parameters with higher precision.