Identifying network motifs that buffer front-to-back signaling in polarized neutrophils.

Identifying network motifs that buffer front-to-back signaling in polarized neutrophils.
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识别缓冲极化中性粒细胞中前后信号传导的网络基序。

DOI:
10.1016/j.celrep.2013.04.009
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发表时间:
2013
期刊:
影响因子:
8.8
通讯作者:
Altschuler,StevenJ
Altschuler,StevenJ
中科院分区:
生物学1区
文献类型:
--
作者:
Wang,Yanqin;Ku,Chin-Jen;Zhang,ElizabethR;Artyukhin,AlexanderB;Weiner,OrionD;Wu,LaniF;Altschuler,StevenJ

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中性粒细胞的极性依赖于局部的相互抑制,将不相容的信号通路隔离到前沿和后缘。相互抑制本身就应该导致细胞具有强大的前锋和弱的后背,反之亦然。然而,对人中性粒细胞细胞间差异的分析表明,尽管前部强度发生了变化,但背部的极性仍然是一致的。这种缓冲是如何实现的?药理扰动和数学模型揭示了微管通过从前到后介导正向长距离串扰来缓冲背极性的功能作用;微管的丢失抑制了缓冲,并导致前后信号之间的反相关。此外,对网络拓扑进行系统的计算搜索后发现,需要一条长距离的正自前向后链路来进行后向缓冲。我们的研究提出了一种可用于极性网络的设计原则:短程相互抑制建立不同的信号区,之后定向的长程激活使一个区域与另一个区域的变化隔离。
Neutrophil polarity relies on local, mutual inhibition to segregate incompatible signaling circuits to the leading and trailing edges. Mutual inhibition alone should lead to cells having strong fronts and weak backs or vice versa. However, analysis of cell-to-cell variation in human neutrophils revealed that back polarity remains consistent despite changes in front strength. How is this buffering achieved? Pharmacological perturbations and mathematical modeling revealed a functional role for microtubules in buffering back polarity by mediating positive, long-range crosstalk from front to back; loss of microtubules inhibits buffering and results in anticorrelation between front and back signaling. Furthermore, a systematic, computational search of network topologies found that a long-range, positive front-to-back link is necessary for back buffering. Our studies suggest a design principle that can be employed by polarity networks: short-range mutual inhibition establishes distinct signaling regions, after which directed long-range activation insulates one region from variations in the other.
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