A conserved GTPase complex gates exocytosis for defence and parasitism across alveolates

IF 18.7 1区生物学 Q1 MICROBIOLOGY

Nature Microbiology Pub Date : 2026-10-02 DOI:10.1038/s41564-026-02501-5

Marta Mendonça Cova, Lucas Morley, Marjorie Maynadier, Jason Delabre, Arnault Graindorge, Laurence Berry-Sterkers, Shrawan Kumar Mageswaran, Valérie Rofidal, Cameron J. Powell, Martin J. Boulanger, Yi-Wei Chang, Daniela Sparvoli, Maryse Lebrun

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Abstract

Regulated protein secretion is a fundamental process by which eukaryotic cells respond to and interact with their dynamic environments, yet its mechanism outside metazoans remains largely unknown. Here we uncover an atypical small GTPase complex (Nd-GTPase–Nd9–NdP1) conserved across the Alveolata—a major eukaryotic clade encompassing ciliates and apicomplexan parasites—that gates organelle exocytosis for diverse functions ranging from cellular defence to host invasion. Using Tetrahymena thermophila and Toxoplasma gondii as comparative models, we combine functional genetics, cryo-electron tomography and integrative structural modelling to show that this complex maintains the organelle secretory apparatus in a pre-secretion state and permits activation upon stimulation. Comparative analysis further reveals that apicomplexan parasites rely on an apical vesicle to tighten control over secretion. These findings define a unifying principle of gated alveolate exocytosis, illustrating how evolution remodels an ancient secretion system to meet specialized cellular demands, and underlie key mechanisms of parasite virulence.

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一个保守的GTPase复合体为防御和跨肺泡的寄生控制胞吐

调节蛋白分泌是真核细胞对其动态环境作出反应和相互作用的基本过程，但其在后生动物外的机制仍不清楚。在这里，我们发现了一种非典型的小GTPase复合物（Nd-GTPase-Nd9-NdP1），这种复合物在肺泡中保守，肺泡是一种主要的真核生物分支，包括纤毛虫和顶复合体寄生虫，它控制细胞器的胞外分泌，具有从细胞防御到宿主入侵的多种功能。以嗜热四膜虫和刚地弓形虫为比较模型，我们结合功能遗传学、低温电子断层扫描和综合结构建模，表明该复合物维持细胞器分泌器官处于分泌前状态，并允许在刺激时激活。对比分析进一步揭示了顶复合体寄生物依靠顶囊加强对分泌物的控制。这些发现定义了门控肺泡胞吐的统一原理，说明了进化如何重塑一个古老的分泌系统以满足特殊的细胞需求，并奠定了寄生虫毒力的关键机制。

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来源期刊

Nature Microbiology Immunology and Microbiology-Microbiology

CiteScore

44.40

自引率

1.10%

发文量

226

期刊介绍： Nature Microbiology aims to cover a comprehensive range of topics related to microorganisms. This includes: Evolution: The journal is interested in exploring the evolutionary aspects of microorganisms. This may include research on their genetic diversity, adaptation, and speciation over time. Physiology and cell biology: Nature Microbiology seeks to understand the functions and characteristics of microorganisms at the cellular and physiological levels. This may involve studying their metabolism, growth patterns, and cellular processes. Interactions: The journal focuses on the interactions microorganisms have with each other, as well as their interactions with hosts or the environment. This encompasses investigations into microbial communities, symbiotic relationships, and microbial responses to different environments. Societal significance: Nature Microbiology recognizes the societal impact of microorganisms and welcomes studies that explore their practical applications. This may include research on microbial diseases, biotechnology, or environmental remediation. In summary, Nature Microbiology is interested in research related to the evolution, physiology and cell biology of microorganisms, their interactions, and their societal relevance.