ActuAtor, a Listeria-inspired molecular tool for physical manipulation of intracellular organizations through de novo actin polymerization.
ActuAtor, a Listeria-inspired molecular tool for physical manipulation of intracellular organizations through de novo actin polymerization.
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ActuAtor，一种受李斯特菌启发的分子工具，用于通过肌动蛋白从头聚合对细胞内组织进行物理操作。
DOI：
10.1016/j.celrep.2023.113089
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Inoue,Takanari
中科院分区：
文献类型：
--
作者：
Nakamura,Hideki;Rho,Elmer;Lee,ChristopherT;Itoh,Kie;Deng,Daqi;Watanabe,Satoshi;Razavi,Shiva;Matsubayashi,HideakiT;Zhu,Cuncheng;Jung,Eleanor;Rangamani,Padmini;Watanabe,Shigeki;Inoue,Takanari
在整个生物学中，形式和功能往往是相互依赖的。在细胞内，线粒体特别吸引了人们的注意，因为它们的形态和功能在病理生理条件下都发生了改变。然而，由于以生理相关方式操纵线粒体形态的局限性，直接评估其因果关系已无法实现。通过工程化细菌肌动蛋白调节因子ActA，我们开发了称为“ActuAtor”的工具，其可诱导地在任意亚细胞位置触发肌动蛋白聚合。ActuAtor介导的肌动蛋白聚合驱动靶细胞器（包括线粒体、高尔基体和细胞核）的显著变形和/或移动。值得注意的是，致动器操作还分散非膜结合实体，例如应力颗粒。然后，我们在功能测定中实施了ActuAtor，发现物理碎片化的线粒体对降解稍微更敏感，而测试的细胞器功能都不是形态依赖性的。ActuAtor的模块化和遗传编码特征应使其能够应用于各种细胞内环境中的形式-功能相互作用的研究。
Form and function are often interdependent throughout biology. Inside cells, mitochondria have particularly attracted attention since both their morphology and functionality are altered under pathophysiological conditions. However, directly assessing their causal relationship has been beyond reach due to the limitations of manipulating mitochondrial morphology in a physiologically relevant manner. By engineering a bacterial actin regulator, ActA, we developed tools termed "ActuAtor" that inducibly trigger actin polymerization at arbitrary subcellular locations. The ActuAtor-mediated actin polymerization drives striking deformation and/or movement of target organelles, including mitochondria, Golgi apparatus, and nucleus. Notably, ActuAtor operation also disperses non-membrane-bound entities such as stress granules. We then implemented ActuAtor in functional assays, uncovering the physically fragmented mitochondria being slightly more susceptible to degradation, while none of the organelle functions tested are morphology dependent. The modular and genetically encoded features of ActuAtor should enable its application in studies of the form-function interplay in various intracellular contexts.