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肌动蛋白和肌动蛋白结合蛋白在锥虫中的新功能

Emerging Functions of Actins and Actin Binding Proteins in Trypanosomatids.

作者信息

Gupta Chhitar M, Ambaru Bindu, Bajaj Rani

机构信息

Institute of Bioinformatics and Applied Biotechnology, Bengaluru, India.

Manipal Academy of Higher Education, Manipal, India.

出版信息

Front Cell Dev Biol. 2020 Oct 9;8:587685. doi: 10.3389/fcell.2020.587685. eCollection 2020.

DOI:10.3389/fcell.2020.587685
PMID:33163497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7581878/
Abstract

Actin is the major protein constituent of the cytoskeleton that performs wide range of cellular functions. It exists in monomeric and filamentous forms, dynamics of which is regulated by a large repertoire of actin binding proteins. However, not much was known about existence of these proteins in trypanosomatids, till the genome sequence data of three important organisms of this class, viz. , , became available. Here, we have reviewed most of the findings reported to date on the intracellular distribution, structure and functions of these proteins and based on them, we have hypothesized some of their functions. The major findings are as follows: (1) All the three organisms encode at least a set of ten actin binding proteins (profilin, twinfilin, ADF/cofilin, CAP/srv2, CAPz, coronin, two myosins, two formins) and one isoform of actin, except that encodes for three formins and several myosins along with four actins. (2) Actin 1 and a few actin binding proteins (ADF/cofilin, profilin, twinfilin, coronin and myosin13 in ; ADF/cofilin, profilin and myosin1 in ; profilin and myosin-F in ) have been identified and characterized. (3) In all the three organisms, actin cytoskeleton has been shown to regulate endocytosis and intracellular trafficking. (4) actin1 has been the most characterized protein among trypanosomatid actins. (5) This protein is localized to the cytoplasm as well as in the flagellum, nucleus and kinetoplast, and , it binds to DNA and displays scDNA relaxing and kDNA nicking activities. (6) The pure protein prefers to form bundles instead of thin filaments, and does not bind DNase1 or phalloidin. (7) Myosin13, myosin1 and myosin-F regulate endocytosis and intracellular trafficking, respectively, in , and . (8) Actin-dependent myosin13 motor is involved in dynamics and assembly of flagellum. (9) twinfilin localizes mostly to the nucleolus and coordinates karyokinesis by effecting splindle elongation and DNA synthesis. (10) coronin binds and promotes actin filament formation and exists in tetrameric form rather than trimeric form, like other coronins. (11) Trypanosomatid profilins are essential for survival of all the three parasites.

摘要

肌动蛋白是细胞骨架的主要蛋白质成分,执行广泛的细胞功能。它以单体和丝状形式存在,其动态变化受大量肌动蛋白结合蛋白的调节。然而,在这一类的三种重要生物体(即 、 、 )的基因组序列数据可用之前,对于这些蛋白质在锥虫中的存在情况了解不多。在这里,我们回顾了迄今为止报道的关于这些蛋白质的细胞内分布、结构和功能的大部分研究结果,并在此基础上对它们的一些功能进行了推测。主要研究结果如下:(1)所有这三种生物体至少编码一组十种肌动蛋白结合蛋白(肌动蛋白解聚因子/丝切蛋白、富含脯氨酸的肌动蛋白结合蛋白、双丝状肌动蛋白、CAP/srv2、肌动蛋白帽蛋白、冠蛋白、两种肌球蛋白、两种formin)和一种肌动蛋白异构体,除了 编码三种formin、几种肌球蛋白以及四种肌动蛋白。(2)已鉴定并表征了肌动蛋白1和一些肌动蛋白结合蛋白( 中的肌动蛋白解聚因子/丝切蛋白、富含脯氨酸的肌动蛋白结合蛋白、双丝状肌动蛋白、冠蛋白和肌球蛋白13; 中的肌动蛋白解聚因子/丝切蛋白、富含脯氨酸的肌动蛋白结合蛋白和肌球蛋白1; 中的富含脯氨酸的肌动蛋白结合蛋白和肌球蛋白-F)。(3)在所有这三种生物体中,肌动蛋白细胞骨架已被证明可调节内吞作用和细胞内运输。(4) 肌动蛋白1是锥虫肌动蛋白中研究最多的蛋白质。(5)这种蛋白质定位于细胞质以及鞭毛、细胞核和动基体中,并且 ,它与DNA结合并表现出单链环状DNA松弛和线粒体DNA切口活性。(6)纯蛋白更倾向于形成束状而不是细纤维,并且不与脱氧核糖核酸酶1或鬼笔环肽结合。(7)肌球蛋白13、肌球蛋白1和肌球蛋白-F分别在 、 和 中调节内吞作用和细胞内运输。(8)依赖肌动蛋白的肌球蛋白13马达参与 鞭毛的动态变化和组装。(9) 双丝状肌动蛋白主要定位于核仁,并通过影响纺锤体伸长和DNA合成来协调核分裂。(10) 冠蛋白结合并促进肌动蛋白丝的形成,并且以四聚体形式存在,而不是像其他冠蛋白那样以三聚体形式存在。(11)锥虫富含脯氨酸的肌动蛋白结合蛋白对所有这三种寄生虫的存活至关重要。

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