Behaviors of individual microtubules and microtubule populations relative to critical concentrations: dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis

Behaviors of individual microtubules and microtubule populations relative to critical concentrations: dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis
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个体微管和微管群相对于临界浓度的行为:当临界浓度因核苷酸水解而分开时,会发生动态不稳定

DOI:
10.1091/mbc.e19-02-0101
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发表时间:
2020
影响因子:
3.3
通讯作者:
Mogilner, Alex
Mogilner, Alex
中科院分区:
生物学3区
文献类型:
--
作者:
Jonasson, Erin M.;Mauro, Ava J.;Li, Chunlei;Labuz, Ellen C.;Mahserejian, Shant M.;Scripture, Jared P.;Gregoretti, Ivan V.;Alber, Mark;Goodson, Holly V.;Mogilner, Alex

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临界浓度(CC)的概念是理解微管(MT)和其他细胞骨架聚合物行为的核心。传统上,这些聚合物被理解为具有一个CC,以多种方式测量,并被认为是聚合物组装所需的亚基浓度。然而,这个框架不包括动态不稳定性(DI),有工作表明,MT有两个CC。我们使用我们以前建立的模拟,以确认MT有(至少)两个实验相关的CC,并澄清个人和群体的行为相对于CC。在游离亚基浓度高于较低CC(CCE伸长)时,单个细丝的生长阶段可以短暂发生;高于较高CC(CCNetAssembly)时,群体的聚合物质量将持续增加。我们的研究结果表明,大多数实验CC测量对应于CCNetAssembly,这意味着“典型的”DI发生在传统上认为聚合物组装所需的浓度以下。我们报告说,[游离微管蛋白]在稳态不等于CCNetAssembly,而是渐近地接近CCNetAssembly [总微管蛋白]的增加,并取决于稳定的MT成核位点的数量。我们发现,CCE longation和CCNetAssembly之间的分离程度取决于核苷酸水解的速率。这个明确的框架有助于解释和统一许多实验观察。
The concept of critical concentration (CC) is central to understanding the behavior of microtubules (MTs) and other cytoskeletal polymers. Traditionally, these polymers are understood to have one CC, measured in multiple ways and assumed to be the subunit concentration necessary for polymer assembly. However, this framework does not incorporate dynamic instability (DI), and there is work indicating that MTs have two CCs. We use our previously established simulations to confirm that MTs have (at least) two experimentally relevant CCs and to clarify the behavior of individuals and populations relative to the CCs. At free subunit concentrations above the lower CC (CCElongation), growth phases of individual filaments can occurtransiently; above the higher CC (CCNetAssembly), the population’s polymer mass will increasepersistently. Our results demonstrate that most experimental CC measurements correspond to CCNetAssembly, meaning that “typical” DI occurs below the concentration traditionally considered necessary for polymer assembly. We report that [free tubulin] at steady state does not equal CCNetAssembly, but instead approaches CCNetAssemblyasymptotically as [total tubulin] increases, and depends on the number of stable MT nucleation sites. We show that the degree of separation between CCElongationand CCNetAssemblydepends on the rate of nucleotide hydrolysis. This clarified framework helps explain and unify many experimental observations.
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