Molecular Parasitology, Department of Biology, University of Bayreuth, Universitätsstr. 30, 95447 Bayreuth, Germany.
Experimental Physics I, Department of Physics, University of Bayreuth, Universitätsstr. 30, 95447 Bayreuth, Germany.
J Cell Sci. 2020 Sep 15;133(18):jcs248047. doi: 10.1242/jcs.248047.
The shape of kinetoplastids, such as , is precisely defined during the stages of the life cycle and governed by a stable subpellicular microtubule cytoskeleton. During the cell cycle and transitions between life cycle stages, this stability has to transiently give way to a dynamic behaviour to enable cell division and morphological rearrangements. How these opposing requirements of the cytoskeleton are regulated is poorly understood. Two possible levels of regulation are activities of cytoskeleton-associated proteins and microtubule post-translational modifications (PTMs). Here, we investigate the functions of two putative tubulin polyglutamylases in , TTLL6A and TTLL12B. Depletion of both proteins leads to a reduction in tubulin polyglutamylation and is associated with disintegration of the posterior cell pole, loss of the microtubule plus-end-binding protein EB1 and alterations of microtubule dynamics. We also observe a reduced polyglutamylation of the flagellar axoneme. Quantitative motility analysis reveals that the PTM imbalance correlates with a transition from directional to diffusive cell movement. These data show that microtubule polyglutamylation has an important role in regulating cytoskeletal architecture and motility in the parasite This article has an associated First Person interview with the first author of the paper.
锥虫类的形态在生命周期的各个阶段都被精确地定义，并受到稳定的亚膜微管细胞骨架的控制。在细胞周期和生命周期阶段之间的转变过程中，这种稳定性必须暂时让位于动态行为，以实现细胞分裂和形态重排。细胞骨架的这些相反要求是如何被调节的，目前还知之甚少。有两种可能的调节方式是细胞骨架相关蛋白的活性和微管翻译后修饰（PTMs）。在这里，我们研究了两种假定的微管多谷氨酰胺酶在 中的功能，TTLL6A 和 TTLL12B。这两种蛋白的耗竭都会导致微管多谷氨酰化的减少，并与后极细胞的解体、微管末端结合蛋白 EB1 的丢失以及微管动力学的改变有关。我们还观察到鞭毛轴丝的多谷氨酰化减少。定量运动分析表明，这种 PTM 失衡与从定向运动到扩散运动的转变相关。这些数据表明，微管多谷氨酰化在调节寄生虫细胞骨架结构和运动方面起着重要作用。本文附有该论文第一作者的第一人称采访。
