Actin and an unconventional myosin motor, TgMyoF, control the organization and dynamics of the endomembrane network in Toxoplasma gondii.

Actin and an unconventional myosin motor, TgMyoF, control the organization and dynamics of the endomembrane network in Toxoplasma gondii.
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肌动蛋白和非常规肌球蛋白马达TgMyoF控制弓形虫内膜网络的组织和动力学。

DOI:
10.1371/journal.ppat.1008787
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发表时间:
2021-03
期刊:
影响因子:
6.7
通讯作者:
Heaslip AT
Heaslip AT
中科院分区:
医学1区
文献类型:
--
作者:
Carmeille R;Schiano Lomoriello P;Devarakonda PM;Kellermeier JA;Heaslip AT

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弓形虫是一种专性细胞内寄生虫,依赖于三种不同的分泌细胞器,即微线体、棒状体和致密颗粒,来维持寄生虫的生存和疾病发病机制。运往这些细胞器的分泌蛋白在内质网 (ER) 中合成,并依次通过由高尔基体和多个高尔基体后区室组成的高度极化的内膜网络进行运输。目前,人们对寄生虫细胞骨架如何控制细胞器在该途径中的定位,或者囊泡货物如何在细胞器之间运输知之甚少。在这里,我们表明,F-肌动蛋白和非常规肌球蛋白运动 TgMyoF 控制分泌途径中细胞器的动力学和组织,特别是内质网小管运动、高尔基体和后高尔基体室的顶端定位、棒状体的顶端定位,以及最后 Rab6 阳性和 Rop1 阳性囊泡的定向运输。因此,本研究确定 TgMyoF 和肌动蛋白是弓形虫内膜系统的关键细胞骨架成分。内膜运输是所有真核细胞中重要的细胞过程。在大多数情况下,分子马达肌球蛋白、驱动蛋白和动力蛋白沿着肌动蛋白和微管丝运输包括囊泡、细胞器和转录物在内的货物,其方式类似于在轨道上行驶的火车。对于单细胞真核生物弓形虫来说,蛋白质通过内膜系统的准确运输对于寄生虫的生存和致病性至关重要。然而,人们对这种寄生虫的货物运输机制知之甚少。在这项研究中,我们荧光标记了多个内膜细胞器,并使用活细胞显微镜对它们的运动进行成像。我们证明丝状肌动蛋白和名为 TgMyoF 的非常规肌球蛋白马达控制细胞器在该途径中的定位以及转运囊泡在整个寄生虫细胞质中的运动。这些数据为了解这种重要病原体的货物运输机制提供了新的见解,并扩展了我们对肌动蛋白在寄生虫生长周期的细胞内阶段中的生物学作用的理解。
Toxoplasma gondii is an obligate intracellular parasite that relies on three distinct secretory organelles, the micronemes, rhoptries, and dense granules, for parasite survival and disease pathogenesis. Secretory proteins destined for these organelles are synthesized in the endoplasmic reticulum (ER) and sequentially trafficked through a highly polarized endomembrane network that consists of the Golgi and multiple post-Golgi compartments. Currently, little is known about how the parasite cytoskeleton controls the positioning of the organelles in this pathway, or how vesicular cargo is trafficked between organelles. Here we show that F-actin and an unconventional myosin motor, TgMyoF, control the dynamics and organization of the organelles in the secretory pathway, specifically ER tubule movement, apical positioning of the Golgi and post-Golgi compartments, apical positioning of the rhoptries, and finally, the directed transport of Rab6-positive and Rop1-positive vesicles. Thus, this study identifies TgMyoF and actin as the key cytoskeletal components that organize the endomembrane system in T. gondii. Endomembrane trafficking is a vital cellular process in all eukaryotic cells. In most cases the molecular motors myosin, kinesin, and dynein transport cargo including vesicles, organelles and transcripts along actin and microtubule filaments in a manner analogous to a train moving on its tracks. For the unicellular eukaryote Toxoplasma gondii, the accurate trafficking of proteins through the endomembrane system is vital for parasite survival and pathogenicity. However, the mechanisms of cargo transport in this parasite are poorly understood. In this study, we fluorescently labeled multiple endomembrane organelles and imaged their movements using live cell microscopy. We demonstrate that filamentous actin and an unconventional myosin motor named TgMyoF control both the positioning of organelles in this pathway and the movement of transport vesicles throughout the parasite cytosol. This data provides new insight into the mechanisms of cargo transport in this important pathogen and expands our understanding of the biological roles of actin in the intracellular phase of the parasite’s growth cycle.
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期刊: The Journal of cell biology
影响因子: --
作者:
Friedman JR;Webster BM;Mastronarde DN;Verhey KJ;Voeltz GK
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