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由……诱导产生的侵入孔

The invasion pore induced by .

作者信息

Kegawa Y, Male F, Jiménez-Munguía I, Blank P S, Mekhedov E, Ward G, Zimmerberg J

机构信息

Section on Integrative Biophysics; Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH).

Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, United States.

出版信息

bioRxiv. 2024 Nov 28:2024.10.11.617945. doi: 10.1101/2024.10.11.617945.

Abstract

Obligate intracellular parasites invade host cells to survive. Following host cell contact, the apicomplexan injects proteins required for invasion into the host cell. Here, electrophysiological recordings of host cells acquired at sub-200 ms resolution allowed detection and analysis of a transient increase in host membrane conductance following exposure to . Transients always preceded invasion but parasites depleted of the moving junction protein RON2 generated transients without invading, ruling out a direct structural role for RON2 in generating the conductance pathway or restricting the diffusion of its components. Time-series analysis developed for transients and applied to the entire transient dataset (910,000 data points) revealed multiple quantal conductance changes in the parasite-induced transient, consistent with a rapid insertion, then slower removal, blocking, or inactivation of pore-like conductance steps. Quantal steps for RH had a principal mode with Gaussian mean of 0.26 nS, similar in step size to the apicomplexan protein translocon EXP2. Without RON2 the quantal mean was significantly different (0.19 nS). Because no invasion occurs without poration, the term 'invasion pore' is proposed.

摘要

专性细胞内寄生虫侵入宿主细胞以存活。在与宿主细胞接触后,顶复门原虫将侵入所需的蛋白质注入宿主细胞。在此,以低于200毫秒的分辨率对宿主细胞进行的电生理记录能够检测和分析暴露于[未提及物质]后宿主细胞膜电导的瞬时增加。瞬时变化总是先于侵入发生,但缺失运动连接蛋白RON2的寄生虫产生了瞬时变化却未发生侵入,这排除了RON2在产生电导途径或限制其成分扩散方面的直接结构作用。为瞬时变化开发并应用于整个瞬时数据集(910,000个数据点)的时间序列分析揭示了寄生虫诱导的瞬时变化中多个量子化电导变化,这与孔状电导步骤的快速插入,然后是较慢的去除、阻断或失活一致。RH的量子化步骤的主要模式的高斯均值为0.26纳安,步长与顶复门原虫蛋白转运体EXP2相似。没有RON2时,量子化均值有显著差异(0.19纳安)。由于没有形成孔就不会发生侵入,因此提出了“侵入孔”这一术语。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e208/11606488/4ec93c713dba/nihpp-2024.10.11.617945v2-f0001.jpg

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