Prieurianin/endosidin 1 is an actin-stabilizing small molecule identified from a chemical genetic screen for circadian clock effectors in Arabidopsis thaliana.
Prieurianin/endosidin 1 is an actin-stabilizing small molecule identified from a chemical genetic screen for circadian clock effectors in Arabidopsis thaliana.
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DOI：
10.1111/j.1365-313x.2012.04991.x
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发表时间：
2012-07
期刊：
影响因子：
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通讯作者：
Réka Tóth;C. Gerding-Reimers;M. Deeks;Sascha Menninger;R. M. Gallegos;I. A. N. Tonaco;Katja Hübel
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文献类型：
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作者：
Réka Tóth;C. Gerding-Reimers;M. Deeks;Sascha Menninger;R. M. Gallegos;I. A. N. Tonaco;Katja Hübel
化学调节剂是研究生物过程的强大工具。为了识别生物钟效应器，我们筛选了模式植物拟南芥中的天然产物库。两种化合物，prieurianin (Pri) 和 prieurianinacetate，被确定会导致昼夜节律缩短。最近，Pri 被独立鉴定为囊泡运输抑制剂，并重新命名为内皮苷 1 (ES1)。在这里，我们表明 Pri 主要影响体内肌动蛋白丝的灵活性，随后导致断裂和丝解聚的减少。肌动蛋白细胞骨架的这种稳定随后导致囊泡运输的变化。 Pri 还影响哺乳动物细胞中的微丝，表明其靶标高度保守；然而，它在体外并没有改变肌动蛋白动力学，这表明其活性需要肌动蛋白相关蛋白的存在。此外，充分表征的肌动蛋白抑制剂以与 Pri 类似的方式缩短了拟南芥时钟的周期长度，支持了 Pri 通过改变肌动蛋白网络影响节律的观点。我们得出的结论是，肌动蛋白相关过程以光依赖性方式影响昼夜节律系统，但它们的破坏并不会消除节律性。总之，我们认为 Pri 的主要作用是稳定肌动蛋白细胞骨架系统，从而影响内体运输。 Pri 似乎通过与之前描述的抑制剂不同的机制来稳定肌动蛋白丝，并将成为研究肌动蛋白相关细胞过程的有用工具。
Chemical modulators are powerful tools to investigate biological processes. To identify circadian clock effectors, we screened a natural product library in the model plant Arabidopsis thaliana. Two compounds, prieurianin (Pri) and prieurianin acetate, were identified as causing a shorter circadian period. Recently, Pri was independently identified as a vesicle trafficking inhibitor and re-named endosidin 1 (ES1). Here we show that Pri primarily affects actin filament flexibility in vivo, later resulting in reduced severing and filament depolymerization. This stabilization of the actin cytoskeleton subsequently causes changes in vesicle trafficking. Pri also affected microfilaments in mammalian cells, indicating that its target is highly conserved; however, it did not alter actin dynamics in vitro, suggesting that its activity requires the presence of actin-associated proteins. Furthermore, well-characterized actin inhibitors shortened the period length of the Arabidopsis clock in a similar way to Pri, supporting the idea that Pri affects rhythms by altering the actin network. We conclude that actin-associated processes influence the circadian system in a light-dependent manner, but their disruption does not abolish rhythmicity. In summary, we propose that the primary effect of Pri is to stabilize the actin cytoskeleton system, thereby affecting endosome trafficking. Pri appears to stabilize actin filaments by a different mechanism from previously described inhibitors, and will be a useful tool to study actin-related cellular processes.