通过多位点磷酸化的多位信息存储
Multi-bit information storage by multisite phosphorylation
摘要：
细胞将信息储存在DNA和稳定的基因表达程序中，从而实现长期细胞记忆的形式。细胞还必须拥有短期形式的信息存储，在事后实施，以识别和解释外部信号。例如，CaMKII被认为实现了在突触后密度下学习所需的一位（one-bit）短期记忆。在这里，我们通过数学分析表明，多位点的蛋白磷酸化，这是无处不在的所有真核生物的信号转导途径，表现出多稳态的最大数量的增加与网站的数量。当n为偶数时，最大信息存储容量至少为log_2（n+2）/2bits;当n为奇数时，最大信息存储容量至少为log_2（n+1）/2bits。此外，当底物过量时，酶饱和连同位点特异性相对催化效率的交替低/高模式一起富集多稳定性。也就是说，在生理上合理的参数范围内，多稳态比单稳态更有可能。我们讨论了在追求这些预测和确定短期信息存储的生物学作用的实验挑战。
英文摘要：
Cells store information in DNA and in stable programs of gene expression, which thereby implement forms of long-term cellular memory. Cells must also possess short-term forms of information storage, implemented post-translationally, to transduce and interpret external signals. CaMKII, for instance, is thought to implement a one-bit (bistable) short-term memory required for learning at post-synaptic densities. Here we show by mathematical analysis that multisite protein phosphorylation, which is ubiquitous in all eukaryotic signalling pathways, exhibits multistability for which the maximal number of steady states increases with the number of sites. If there are n sites, the maximal information storage capacity is at least log_2 (n+2)/2 bits when n is even and log_2 (n+1)/2 bits when n is odd. Furthermore, when substrate is in excess, enzyme saturation together with an alternating low/high pattern in the site-specific relative catalytic efficiencies, enriches for multistability. That is, within physiologically plausible ranges for parameters, multistability becomes more likely than monostability. We discuss the experimental challenges in pursuing these predictions and in determining the biological role of short-term information storage.
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