Abstract
Plants both lose water and take in carbon dioxide through microscopic stomatal pores, each of which is regulated by a surrounding pair of guard cells. During drought, the plant hormone abscisic acid (ABA) inhibits stomatal opening and promotes stomatal closure, thereby promoting water conservation. Dozens of cellular components have been identified to function in ABA regulation of guard cell volume and thus of stomatal aperture, but a dynamic description is still not available for this complex process. Here we synthesize experimental results into a consistent guard cell signal transduction network for ABA-induced stomatal closure, and develop a dynamic model of this process. Our model captures the regulation of more than 40 identified network components, and accords well with previous experimental results at both the pathway and whole-cell physiological level. By simulating gene disruptions and pharmacological interventions we find that the network is robust against a significant fraction of possible perturbations. Our analysis reveals the novel predictions that the disruption of membrane depolarizability, anion efflux, actin cytoskeleton reorganization, cytosolic pH increase, the phosphatidic acid pathway, or K+ efflux through slowly activating K+ channels at the plasma membrane lead to the strongest reduction in ABA responsiveness. Initial experimental analysis assessing ABA-induced stomatal closure in the presence of cytosolic pH clamp imposed by the weak acid butyrate is consistent with model prediction. Simulations of stomatal response as derived from our model provide an efficient tool for the identification of candidate manipulations that have the best chance of conferring increased drought stress tolerance and for the prioritization of future wet bench analyses. Our method can be readily applied to other biological signaling networks to identify key regulatory components in systems where quantitative information is limited.
Highlights
One central challenge of systems biology is the distillation of systems level information into applications such as drug discovery in biomedicine or genetic modification of crops
Extraction and Organization of Data from the Literature We focus on abscisic acid (ABA) induction of stomatal closure, rather than ABA inhibition of stomatal opening, because these two processes, related, exhibit distinct mechanisms, and there is substantially more information on the former process than on the latter in the literature
The ethyl methanesulfonate–generated ost1 mutant is less sensitive to ABA; one can infer that the OST1 protein is a part of the ABA signaling cascade [12]
Summary
One central challenge of systems biology is the distillation of systems level information into applications such as drug discovery in biomedicine or genetic modification of crops. High-throughput experimental methods have enabled the construction of genome-scale maps of transcription factor–DNA and protein–protein interactions [4,5]. The former are quantitative, dynamic descriptions of experimentally well-studied cellular pathways with relatively few components, while the latter are static maps of potential interactions with no information about their timing or kinetics. We introduce a novel approach that stands in the middle ground of the abovementioned methods by incorporating the synthesis and dynamic modeling of complex cellular networks that contain diverse, yet only qualitatively known regulatory interactions
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