机械耦合协调微管生长。

Mechanical coupling coordinates microtubule growth.

作者信息

Leeds Bonnibelle K, Kostello Katelyn F, Liu Yuna Y, Nelson Christian R, Biggins Sue, Asbury Charles L

机构信息

Physiology & Biophysics Department, University of Washington School of Medicine, Seattle WA, USA.

Fred Hutchinson Cancer Research Center.

出版信息

bioRxiv. 2023 Oct 17:2023.06.29.547092. doi: 10.1101/2023.06.29.547092.

Abstract

During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to behave as a single unit. This exquisite coordination might be achieved biochemically, via selective binding of polymerases and depolymerases, or mechanically, because k-fiber microtubules are coupled through a shared load that influences their growth. Here, we use a novel dual laser trap assay to show that microtubule pairs growing are coordinated by mechanical coupling. Kinetic analyses show that microtubule growth is interrupted by stochastic, force-dependent pauses and indicate persistent heterogeneity in growth speed during non-pauses. A simple model incorporating both force-dependent pausing and persistent growth speed heterogeneity explains the measured coordination of microtubule pairs without any free fit parameters. Our findings illustrate how microtubule growth may be synchronized during mitosis and provide a basis for modeling k-fiber bundles with three or more microtubules, as found in many eukaryotes.

摘要

在有丝分裂过程中,附着在动粒上的微管形成束状结构(动粒微管纤维),其中许多微管丝几乎完美同步地生长和缩短,以使每条染色体排列并分离。然而,单个微管的生长速率本质上是可变的,而动粒微管纤维要作为一个单一单元发挥作用,其生长速率必须受到严格调控。这种精确的协调可能通过生化方式实现,即通过聚合酶和解聚酶的选择性结合,或者通过机械方式实现,因为动粒微管纤维中的微管通过共同的负载相互耦合,从而影响它们的生长。在这里,我们使用一种新型的双激光阱测定法来表明,正在生长的微管对是通过机械耦合实现协调的。动力学分析表明,微管的生长会被随机的、力依赖的停顿打断,并且表明在非停顿期间生长速度存在持续的异质性。一个包含力依赖停顿和持续生长速度异质性的简单模型,无需任何自由拟合参数就能解释所测量的微管对的协调性。我们的研究结果阐明了有丝分裂期间微管生长可能是如何同步的,并为模拟许多真核生物中发现的具有三根或更多微管的动粒微管纤维束提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d6/10614740/2ff968c4ecbe/nihpp-2023.06.29.547092v2-f0004.jpg

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