A new discrete dynamic model of ABA-induced stomatal closure predicts key feedback loops

Réka Albert, Biswa R. Acharya, Byeong Wook Jeon, Jorge G.T. Zañudo, Mengmeng Zhu, Karim Osman, Sarah M. Assmann

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Stomata, microscopic pores in leaf surfaces through which water loss and carbon dioxide uptake occur, are closed in response to drought by the phytohormone abscisic acid (ABA). This process is vital for drought tolerance and has been the topic of extensive experimental investigation in the last decades. Although a core signaling chain has been elucidated consisting of ABA binding to receptors, which alleviates negative regulation by protein phosphatases 2C (PP2Cs) of the protein kinase OPEN STOMATA 1 (OST1) and ultimately results in activation of anion channels, osmotic water loss, and stomatal closure, over 70 additional components have been identified, yet their relationships with each other and the core components are poorly elucidated. We integrated and processed hundreds of disparate observations regarding ABA signal transduction responses underlying stomatal closure into a network of 84 nodes and 156 edges and, as a result, established those relationships, including identification of a 36-node, strongly connected (feedback-rich) component as well as its in- and out-components. The network’s domination by a feedback-rich component may reflect a general feature of rapid signaling events. We developed a discrete dynamic model of this network and elucidated the effects of ABA plus knockout or constitutive activity of 79 nodes on both the outcome of the system (closure) and the status of all internal nodes. The model, with more than 10 24 system states, is far from fully determined by the available data, yet model results agree with existing experiments in 82 cases and disagree in only 17 cases, a validation rate of 75%. Our results reveal nodes that could be engineered to impact stomatal closure in a controlled fashion and also provide over 140 novel predictions for which experimental data are currently lacking. Noting the paucity of wet-bench data regarding combinatorial effects of ABA and internal node activation, we experimentally confirmed several predictions of the model with regard to reactive oxygen species, cytosolic Ca 2+ (Ca 2+ c ), and heterotrimeric G-protein signaling. We analyzed dynamics-determining positive and negative feedback loops, thereby elucidating the attractor (dynamic behavior) repertoire of the system and the groups of nodes that determine each attractor. Based on this analysis, we predict the likely presence of a previously unrecognized feedback mechanism dependent on Ca 2+ c . This mechanism would provide model agreement with 10 additional experimental observations, for a validation rate of 85%. Our research underscores the importance of feedback regulation in generating robust and adaptable biological responses. The high validation rate of our model illustrates the advantages of discrete dynamic modeling for complex, nonlinear systems common in biology.

Original languageEnglish (US)
Article numbere2003451
JournalPLoS biology
Volume15
Issue number9
DOIs
StatePublished - Sep 22 2017

Fingerprint

Abscisic Acid
dynamic models
abscisic acid
Dynamic models
Feedback
Droughts
Drought
Heterotrimeric GTP-Binding Proteins
Chemical activation
Aquaporins
Plant Growth Regulators
Signal transduction
prediction
Water
Carbon Dioxide
Phosphoprotein Phosphatases
Protein Kinases
Anions
Reactive Oxygen Species
Signal Transduction

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Albert, Réka ; Acharya, Biswa R. ; Jeon, Byeong Wook ; Zañudo, Jorge G.T. ; Zhu, Mengmeng ; Osman, Karim ; Assmann, Sarah M. / A new discrete dynamic model of ABA-induced stomatal closure predicts key feedback loops. In: PLoS biology. 2017 ; Vol. 15, No. 9.
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abstract = "Stomata, microscopic pores in leaf surfaces through which water loss and carbon dioxide uptake occur, are closed in response to drought by the phytohormone abscisic acid (ABA). This process is vital for drought tolerance and has been the topic of extensive experimental investigation in the last decades. Although a core signaling chain has been elucidated consisting of ABA binding to receptors, which alleviates negative regulation by protein phosphatases 2C (PP2Cs) of the protein kinase OPEN STOMATA 1 (OST1) and ultimately results in activation of anion channels, osmotic water loss, and stomatal closure, over 70 additional components have been identified, yet their relationships with each other and the core components are poorly elucidated. We integrated and processed hundreds of disparate observations regarding ABA signal transduction responses underlying stomatal closure into a network of 84 nodes and 156 edges and, as a result, established those relationships, including identification of a 36-node, strongly connected (feedback-rich) component as well as its in- and out-components. The network’s domination by a feedback-rich component may reflect a general feature of rapid signaling events. We developed a discrete dynamic model of this network and elucidated the effects of ABA plus knockout or constitutive activity of 79 nodes on both the outcome of the system (closure) and the status of all internal nodes. The model, with more than 10 24 system states, is far from fully determined by the available data, yet model results agree with existing experiments in 82 cases and disagree in only 17 cases, a validation rate of 75{\%}. Our results reveal nodes that could be engineered to impact stomatal closure in a controlled fashion and also provide over 140 novel predictions for which experimental data are currently lacking. Noting the paucity of wet-bench data regarding combinatorial effects of ABA and internal node activation, we experimentally confirmed several predictions of the model with regard to reactive oxygen species, cytosolic Ca 2+ (Ca 2+ c ), and heterotrimeric G-protein signaling. We analyzed dynamics-determining positive and negative feedback loops, thereby elucidating the attractor (dynamic behavior) repertoire of the system and the groups of nodes that determine each attractor. Based on this analysis, we predict the likely presence of a previously unrecognized feedback mechanism dependent on Ca 2+ c . This mechanism would provide model agreement with 10 additional experimental observations, for a validation rate of 85{\%}. Our research underscores the importance of feedback regulation in generating robust and adaptable biological responses. The high validation rate of our model illustrates the advantages of discrete dynamic modeling for complex, nonlinear systems common in biology.",
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A new discrete dynamic model of ABA-induced stomatal closure predicts key feedback loops. / Albert, Réka; Acharya, Biswa R.; Jeon, Byeong Wook; Zañudo, Jorge G.T.; Zhu, Mengmeng; Osman, Karim; Assmann, Sarah M.

In: PLoS biology, Vol. 15, No. 9, e2003451, 22.09.2017.

Research output: Contribution to journalArticle

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AU - Albert, Réka

AU - Acharya, Biswa R.

AU - Jeon, Byeong Wook

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