Accurate encoding and decoding by single cells: amplitude versus frequency modulation.
Accurate encoding and decoding by single cells: amplitude versus frequency modulation.
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DOI：
10.1371/journal.pcbi.1004222
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发表时间：
2015-06
影响因子：
4.3
通讯作者：
Endres RG
中科院分区：
文献类型：
--
作者：
Micali G;Aquino G;Richards DM;Endres RG
细胞感知外部浓度，并通过生物化学信号传导，通过调节靶蛋白的表达作出反应。在信号网络和基因调控中，有两种主要的机制可以内部编码浓度：幅度调制（AM），其中内部信号分子的绝对浓度编码刺激，以及频率调制（FM），其中连续爆发之间的周期代表刺激。虽然这两种机制都在生物系统中被观察到，但何时使用AM或FM对细胞有益的问题在很大程度上没有答案。在这里，我们首先考虑一个简单的模型，一个单一的受体（或离子通道），它可以连续信号时，一个配体被绑定，或产生一个突发信号分子受体结合。我们发现，突发信号比连续信号更准确，只有足够快的动态。这表明基于爆发的调制可能在信号网络中比在基因调控中更常见。然后，我们将我们的模型扩展到多个受体，其中连续和突发信号分别相当于AM和FM，发现AM总是更准确。这意味着一些细胞使用FM的原因与准确性以外的因素有关，例如协调多个基因表达或实现阈值交叉机制的能力。信号和信息通常可以通过幅度（AM）或频率（FM）调制来传输，例如，自20世纪30年代以来在无线电波传输中所使用的。已知这两种类型的调制在生物学中发挥作用，AM通常与信号传导和基因表达相关，FM用于在神经元之间的大距离上可靠地传输电信号。令人惊讶的是，FM最近也在基因调控中被观察到，使得它们的作用不如以前认为的那么明显。尽管AM和FM的工程优点和缺点已经得到很好的理解，但生物系统中的等效问题在很大程度上仍未解决。在这里，我们提出了一个简单的模型，信号通过受体（或离子通道）与随后的基因调控，从而实现AM和FM在不同类型的生物途径。然后，我们比较目标蛋白质生产的准确性。我们发现，FM可以更准确地比AM只为一个单一的受体与快速信号，而AM是更准确的慢基因调控和多个受体的信号。最后，我们提出了可能的原因，细胞使用FM，尽管潜在的准确性下降。
Cells sense external concentrations and, via biochemical signaling, respond by regulating the expression of target proteins. Both in signaling networks and gene regulation there are two main mechanisms by which the concentration can be encoded internally: amplitude modulation (AM), where the absolute concentration of an internal signaling molecule encodes the stimulus, and frequency modulation (FM), where the period between successive bursts represents the stimulus. Although both mechanisms have been observed in biological systems, the question of when it is beneficial for cells to use either AM or FM is largely unanswered. Here, we first consider a simple model for a single receptor (or ion channel), which can either signal continuously whenever a ligand is bound, or produce a burst in signaling molecule upon receptor binding. We find that bursty signaling is more accurate than continuous signaling only for sufficiently fast dynamics. This suggests that modulation based on bursts may be more common in signaling networks than in gene regulation. We then extend our model to multiple receptors, where continuous and bursty signaling are equivalent to AM and FM respectively, finding that AM is always more accurate. This implies that the reason some cells use FM is related to factors other than accuracy, such as the ability to coordinate expression of multiple genes or to implement threshold crossing mechanisms. Signals, and hence information, can generally be transmitted either by amplitude (AM) or frequency (FM) modulation, as used, for example, in the transmission of radio waves since the 1930s. Both types of modulation are known to play a role in biology with AM conventionally associated with signaling and gene expression, and FM used to reliably transmit electrical signals over large distances between neurons. Surprisingly, FM was recently also observed in gene regulation, making their roles less distinct than previously thought. Although the engineering advantages and disadvantages of AM and FM are well understood, the equivalent question in biological systems is still largely unsolved. Here, we propose a simple model of signaling by receptors (or ion channels) with subsequent gene regulation, thus implementing both AM and FM in different types of biological pathways. We then compare the accuracy in the production of target proteins. We find that FM can be more accurate than AM only for a single receptor with fast signaling, whereas AM is more accurate in slow gene regulation and with signaling by multiple receptors. Finally, we propose possible reasons that cells use FM despite the potential decrease in accuracy.
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