The Dynamics of Aerotaxis in a Simple Eukaryotic Model.
The Dynamics of Aerotaxis in a Simple Eukaryotic Model.
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DOI：
10.3389/fcell.2021.720623
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发表时间：
2021
影响因子：
5.5
通讯作者：
Pergolizzi B
中科院分区：
文献类型：
--
作者：
Biondo M;Panuzzo C;Ali SM;Bozzaro S;Osella M;Bracco E;Pergolizzi B
在有氧生物中，氧气是高效能量生产所必需的，它是线粒体电子传递链的最后受体，也是基因表达的调节剂。然而，过量的氧气会导致有害活性氧的产生。因此，单细胞或细胞团从缺氧区向最佳氧浓度区定向迁移，称为趋氧性，可以被认为是一种适应性机制，在生物和病理过程中起着重要作用。一个相关的例子是当肿瘤生长超出其血管供应时O2梯度的发展，经常导致转移。在高等真核生物中，亲和性直到最近才开始被探索，但适合解剖这一过程的遗传适应性模式生物仍然是一个未满足的需求。在这方面，我们试图评估Dictyostelium细胞是否可以感知氧梯度并在其响应中定向移动，Dictyostelium细胞是趋化性和其他运动过程的既定模型。通过评估不同的物理参数，我们的研究结果表明，在缺氧条件下，生长和饥饿的盘基ostelium细胞都向更高的O2浓度区域定向迁移。这种迁移的特点是细胞排列的特定模式。在细胞团中形成一个增厚的高细胞密度的圆形锋（电晕），并随着氧梯度持续移动。在缺氧更严重的集落中心，细胞的活动性较差，呈圆形。聚集能力强的细胞通过趋化形成流，当被限制在缺氧条件下时，会发生流或聚集体破碎，产生多个小的松散聚集体，这些聚集体协调地向氧气浓度较高的区域移动。通过测试一组趋化信号缺陷突变体和过氧化氢酶缺陷菌株，我们发现后者和pkbR1null表现出改变的迁移模式。我们的研究结果表明，与哺乳动物细胞一样，盘齿龙细胞内过氧化氢的积累有利于向最佳氧浓度迁移。此外，与趋化性不同，这种氧驱动的迁移是一个不依赖于G蛋白的过程。
In aerobic organisms, oxygen is essential for efficient energy production, and it acts as the last acceptor of the mitochondrial electron transport chain and as regulator of gene expression. However, excessive oxygen can lead to production of deleterious reactive oxygen species. Therefore, the directed migration of single cells or cell clumps from hypoxic areas toward a region of optimal oxygen concentration, named aerotaxis, can be considered an adaptive mechanism that plays a major role in biological and pathological processes. One relevant example is the development of O2 gradients when tumors grow beyond their vascular supply, leading frequently to metastasis. In higher eukaryotic organisms, aerotaxis has only recently begun to be explored, but genetically amenable model organisms suitable to dissect this process remain an unmet need. In this regard, we sought to assess whether Dictyostelium cells, which are an established model for chemotaxis and other motility processes, could sense oxygen gradients and move directionally in their response. By assessing different physical parameters, our findings indicate that both growing and starving Dictyostelium cells under hypoxic conditions migrate directionally toward regions of higher O2 concentration. This migration is characterized by a specific pattern of cell arrangement. A thickened circular front of high cell density (corona) forms in the cell cluster and persistently moves following the oxygen gradient. Cells in the colony center, where hypoxia is more severe, are less motile and display a rounded shape. Aggregation-competent cells forming streams by chemotaxis, when confined under hypoxic conditions, undergo stream or aggregate fragmentation, giving rise to multiple small loose aggregates that coordinately move toward regions of higher O2 concentration. By testing a panel of mutants defective in chemotactic signaling, and a catalase-deficient strain, we found that the latter and the pkbR1null exhibited altered migration patterns. Our results suggest that in Dictyostelium, like in mammalian cells, an intracellular accumulation of hydrogen peroxide favors the migration toward optimal oxygen concentration. Furthermore, differently from chemotaxis, this oxygen-driven migration is a G protein-independent process.
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影响因子：
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作者：
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通讯作者：
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