Tuning chemotactic responses with synthetic multivalent ligands
Tuning chemotactic responses with synthetic multivalent ligands
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DOI：
10.1016/s1074-5521(00)00002-8
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发表时间：
2000-08-01
影响因子：
--
通讯作者：
Kiessling, LL
中科院分区：
文献类型：
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作者：
Gestwicki, JE;Strong, LE;Kiessling, LL
背景：多价配体先前已被用于研究配体价和受体聚集在引发生物反应中的作用。然而，多价配体功能的研究通常采用二价配体或价不明的配体。细胞如何对不同价的多价配体作出反应，这些配体可以在不同程度上聚集一个信号受体，从未被研究过。细菌中介导趋化反应的化学感受器是局部的，聚类被认为在其功能中起作用。利用多价配体直接作用于化学感受器，我们假设我们可以利用配体的价来控制受体的占据和聚集，并最终。细胞反应。结果：为了研究配体价对细菌趋化反应的影响，我们通过开环复分解聚合生成了一系列具有不同价的线性多价阵列。我们报道这些合成配体在大肠杆菌和枯草芽孢杆菌中引起细菌趋化性。趋化反应取决于配体的配价；细菌的反应可以通过改变化学引诱剂配体的配价而改变。值得注意的是，这些趋化反应的差异与多价配体在质膜聚集化学受体的能力有关。结论：我们的研究结果表明配体价可以用来调节细菌的趋化反应。这种调节模式可能源于受体占据的变化或受体聚集的变化，或两者兼而有之。我们的数据暗示受体聚类的变化是改变细胞反应的一个重要机制。考虑到细胞表面受体空间接近度的变化所调节的不同事件，我们的研究结果提出了调节生物反应的一般策略。
Background: Multivalent ligands have been used previously to investigate the role of ligand valency and receptor clustering in eliciting biological responses. Studies of multivalent ligand function, however, typically have employed divalent ligands or ligands of undefined valency. How cells respond to multivalent ligands of distinct valencies, which can cluster a signaling receptor to different extents, has never been examined. The chemoreceptors, which mediate chemotactic responses in bacteria, are localized, and clustering has been proposed to play a role in their function. Using multivalent ligands directed at the chemoreceptors, we hypothesized that we could exploit ligand valency to control receptor occupation and clustering and, ultimately. the cellular response.Results: To investigate the effects of ligand valency on the bacterial chemotactic response, we generated a series of linear multivalent arrays with distinct valencies by ring-opening metathesis polymerization. We report that these synthetic ligands elicit bacterial chemotaxis in both Escherichia coli and Bacillus subtilis. The chemotactic response depended on the valency of the ligand; the response of the bacteria can be altered by varying chemoattractant ligand valency. Significantly, these differences in chemotactic responses were related to the ability of the multivalent ligands to cluster chemoreceptors at the plasma membrane.Conclusions: Our results demonstrate that ligand valency can be used to tune the chemotactic responses of bacteria. This mode of regulation may arise from changes in receptor occupation or changes in receptor clustering or both. Our data implicate changes in receptor clustering as one important mechanism for altering cellular responses. Given the diverse events modulated by changes in the spatial proximity of cell surface receptors, our results suggest a general strategy for tuning biological responses.