Regulation of microtubule disassembly by spatially heterogeneous patterns of acetylation,Soft Matter

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Regulation of microtubule disassembly by spatially heterogeneous patterns of acetylation
Soft Matter ( IF 2.9 ) Pub Date : 2020/02/28 , DOI: 10.1039/c9sm02198a
Aparna J. S. _{1,

2,

3,

4} , Ranjith Padinhateeri _{2,

3,

4,

5} , Dibyendu Das _{2,

3,

4,

6}

Affiliation

Microtubules (MTs) are bio-polymers, composed of tubulin proteins, involved in several functions such as cell division, transport of cargoes within cells, maintaining cellular structures etc. Their kinetics are often affected by chemical modifications on the filament known as Post Translational Modifications (PTMs). Acetylation is a PTM which occurs on the luminal surface of the MT lattice and has been observed to reduce the lateral interaction between tubulins on adjacent protofilaments. Depending on the properties of the acetylase enzyme αTAT1 and the structural features of MTs, the patterns of acetylation formed on MTs are observed to be quite diverse. In this study, we present a multi-protofilament model with spatially heterogeneous patterns of acetylation, and investigate how the local kinetic differences arising from heterogeneity affect the global kinetics of MT filaments. From the computational study we conclude that a filament with spatially uniform acetylation is least stable against disassembly, while ones with more clustered acetylation patterns may provide better resistance against disassembly. The increase in disassembly times for clustered pattern as compared to uniform pattern can be up to fifty percent for identical amounts of acetylation. Given that acetylated MTs affect several cellular functions as well as diseases such as cancer, our study indicates that spatial patterns of acetylation need to be focused on, apart from the overall amount of acetylation.

中文翻译：

通过空间异质性乙酰化模式调节微管拆卸

微管（MTs）是由微管蛋白组成的生物聚合物，涉及多种功能，例如细胞分裂，细胞内货物运输，维持细胞结构等。它们的动力学通常受丝上化学修饰（称为翻译后修饰（PTM））的影响。乙酰化是一种PTM，它发生在MT晶格的腔表面上，并且已观察到可减少相邻原丝上微管蛋白之间的横向相互作用。根据乙酰酶αTAT1的特性和MT的结构特征，观察到MT上形成的乙酰化模式非常多样。在这项研究中，我们提出了一个具有空间异质性乙酰化模式的多原丝模型，并研究了异质性引起的局部动力学差异如何影响MT细丝的整体动力学。根据计算研究，我们得出结论，具有空间均匀乙酰化作用的长丝对拆卸的稳定性最差，而具有更多簇状乙酰化模式的那些可能提供更好的抗拆卸性。对于相同数量的乙酰化，与均匀图案相比，簇状图案的拆卸时间最多可增加百分之五十。考虑到乙酰化的MT会影响多种细胞功能以及诸如癌症等疾病，因此我们的研究表明，除了乙酰化的总量外，乙酰化的空间模式还需要关注。

更新日期：2020-03-26

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