The invasion pore induced by Toxoplasma gondii.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-09-19 DOI:10.1038/s44319-025-00565-8

Yuto Kegawa, Frances Male, Irene Jiménez-Munguía, Paul S Blank, Elena Mekhedov, Gary E Ward, Joshua Zimmerberg

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Abstract

The parasite Toxoplasma gondii invades its host cell only after secreting proteins such as invasion-requisite RON2 that inserts into the host cell membrane to establish the moving junction. Electrophysiological recordings at sub-200 µs resolution show a transient increase in host cell membrane conductance following parasite exposure. Transients always precede invasion, but parasites depleted of RON2 generate transients without invading. Thus RON2 is not essential for transient generation. Time-series analysis developed here and applied to the 910,000 data point transient dataset reveal multiple quantal conductance changes in the parasite-induced transient, consistent with rapid insertion, then slower removal, blocking, or inactivation of potential pore components. Quantal steps for wild-type RH strain parasites have a principal mode with Gaussian mean of 0.26 nS, similar in step size to the pore forming protein EXP2, part of the PTEX translocon of malaria parasites. Without RON2 the quantal mean (0.19 nS) is significantly different. Because we observe no parasite invasion without poration, the term "invasion pore" is proposed to describe this transient breach in host cell membrane barrier integrity during invasion.

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刚地弓形虫诱导的侵袭孔。

刚地弓形虫只有在分泌入侵必需的蛋白质（如插入宿主细胞膜建立移动连接的RON2）后才会入侵宿主细胞。在低于200µs分辨率下的电生理记录显示，暴露于寄生虫后，宿主细胞膜电导率瞬间增加。暂态总是在入侵之前发生，但缺乏RON2的寄生虫产生暂态而不入侵。因此，RON2对于瞬态发电不是必需的。本文开发的时间序列分析并应用于910,000个数据点的瞬态数据集，揭示了寄生虫诱导的瞬态中多重量子电导的变化，与快速插入，然后缓慢移除，阻塞或失活潜在孔隙成分一致。野生型RH菌株寄生虫的量子步长与疟原虫PTEX易位的孔形成蛋白EXP2的步长相似，其主模式的高斯平均值为0.26 nS。在没有RON2的情况下，量子平均值（0.19 nS）有显著差异。由于我们观察到没有一种寄生虫的入侵是没有孔的，所以我们提出了“入侵孔”一词来描述入侵过程中宿主细胞膜屏障完整性的短暂破坏。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.