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微纳尺度时空解析弓形虫滑行运动的黏附策略。

Submicrometre spatiotemporal characterization of the Toxoplasma adhesion strategy for gliding motility.

机构信息

Institute for Advanced Biosciences, Biomechanics of Host-Parasite Cell Interactions Team, CNRS UMR 5309, INSERM U1209, Université Grenoble Alpes, Grenoble, France.

Laboratoire Interdisciplinaire de Physique, CNRS UMR 5588, Université Grenoble Alpes, Grenoble, France.

出版信息

Nat Microbiol. 2024 Dec;9(12):3148-3164. doi: 10.1038/s41564-024-01818-3. Epub 2024 Nov 4.

DOI:10.1038/s41564-024-01818-3
PMID:39496912
Abstract

Toxoplasma gondii is a protozoan apicomplexan parasite that uses an adhesion-dependent mode of motility termed gliding to access host cells and disseminate into tissues. Previous studies on Apicomplexa motile morphotypes, including the T. gondii tachyzoite, have identified a cortical actin-myosin motor system that drives the rearward translocation of transmembrane adhesins, thus powering forward movement. However, this model is currently questioned. Here, combining micropatterning and tunable surface chemistry (to edit parasite surface ligands) with flow force and live or super-resolution imaging, we show that tachyzoites build only one apical anchoring contact with the substrate, over which it slides. Furthermore, we show that glycosaminoglycan-parasite interactions are sufficient to promote such force-productive contact and find that the apicobasal flow is set up independent of adhesin release and surface interactions. These findings should enable further characterization of the molecular functions at the T. gondii-substrate mechanosensitive interface and their comparison across apicomplexans.

摘要

刚地弓形虫是一种原生质顶复门顶复体寄生虫,它使用一种依赖黏附的运动模式——滑行,来进入宿主细胞并扩散到组织中。以前对顶复门运动形态的研究,包括刚地弓形虫速殖子,已经确定了一个皮质肌动球蛋白马达系统,该系统驱动跨膜黏附物的向后易位,从而为向前运动提供动力。然而,目前这个模型受到了质疑。在这里,我们结合微图案化和可调表面化学(编辑寄生虫表面配体)与流动力和实时或超分辨率成像,表明速殖子只与底物建立一个顶端锚定接触点,然后在其上滑动。此外,我们还表明,糖胺聚糖-寄生虫相互作用足以促进这种产生力的接触,并且发现顶端-基底流的建立独立于黏附物的释放和表面相互作用。这些发现应该能够进一步表征刚地弓形虫-底物机械敏感界面的分子功能,并在顶复门中进行比较。

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