Multi-level Modeling of Light-Induced Stomatal Opening Offers New Insights into Its Regulation by Drought

Plant guard cells gate CO2 uptake and transpirational water loss through stomatal pores. As a result of decades of experimental investigation, there is an abundance of information on the involvement of specific proteins and secondary messengers in the regulation of stomatal movements and on the pairwise relationships between guard cell components. We constructed a multi-level dynamic model of guard cell signal transduction during light-induced stomatal opening and of the effect of the plant hormone abscisic acid (ABA) on this process. The model integrates into a coherent network the direct and indirect biological evidence regarding the regulation of seventy components implicated in stomatal opening. Analysis of this signal transduction network identified robust cross-talk between blue light and ABA, in which [Ca2+]c plays a key role, and indicated an absence of cross-talk between red light and ABA. The dynamic model captured more than 1031 distinct states for the system and yielded outcomes that were in qualitative agreement with a wide variety of previous experimental results. We obtained novel model predictions by simulating single component knockout phenotypes. We found that under white light or blue light, over 60%, and under red light, over 90% of all simulated knockouts had similar opening responses as wild type, showing that the system is robust against single node loss. The model revealed an open question concerning the effect of ABA on red light-induced stomatal opening. We experimentally showed that ABA is able to inhibit red light-induced stomatal opening, and our model offers possible hypotheses for the underlying mechanism, which point to potential future experiments. Our modelling methodology combines simplicity and flexibility with dynamic richness, making it well suited for a wide class of biological regulatory systems.植物保卫细胞通过气孔孔隙调控二氧化碳吸收与蒸腾失水过程。历经数十年的实验研究，学界已积累了大量关于特定蛋白质与第二信使参与气孔运动调控，以及保卫细胞各组分间成对调控关系的研究数据。我们构建了光诱导气孔开放过程中保卫细胞信号转导的多层次动态模型，以及植物激素脱落酸（abscisic acid, ABA）对该过程的调控效应模型。该模型将与气孔开放相关的70种组分的调控相关直接与间接生物学证据整合为一个连贯的调控网络。对该信号转导网络的分析揭示了蓝光与脱落酸之间存在显著的信号串扰，其中[Ca²⁺]c发挥关键调控作用，同时发现红光与脱落酸之间不存在信号串扰。该动态模型可表征该系统超过10³¹种不同状态，其预测结果与大量既往实验结果在定性层面高度一致。我们通过模拟单组分敲除表型，获得了多项全新的模型预测结果。研究发现，在白光或蓝光条件下，超过60%的模拟敲除样本与野生型的气孔开放响应一致；在红光条件下，该比例超过90%，表明该系统对单节点缺失具有较强鲁棒性。该模型还揭示了一个关于脱落酸对红光诱导气孔开放调控效应的待解科学问题。我们通过实验证实脱落酸能够抑制红光诱导的气孔开放，本模型为该调控过程的潜在分子机制提供了可行假说，可为未来相关实验研究指明方向。我们的建模方法兼具简洁性、灵活性与动态丰富性，可广泛适用于各类生物调控系统。