More Like this

1. Modeling and analysis of the macronutrient signaling network in budding yeast

   https://doi.org/10.1091/mbc.E20-02-0117  

   Jalihal, Amogh P.; Kraikivski, Pavel; Murali, T. M.; Tyson, John J. (November 2021, Molecular Biology of the Cell)

   Edelstein-Keshet, Leah (Ed.)

   Adaptive modulation of the global cellular growth state of unicellular organisms is crucial for their survival in fluctuating nutrient environments. Because these organisms must be able to respond reliably to ever varying and unpredictable nutritional conditions, their nutrient signaling networks must have a certain inbuilt robustness. In eukaryotes, such as the budding yeast Saccharomyces cerevisiae, distinct nutrient signals are relayed by specific plasma membrane receptors to signal transduction pathways that are interconnected in complex information-processing networks, which have been well characterized. However, the complexity of the signaling network confounds the interpretation of the overall regulatory “logic” of the control system. Here, we propose a literature-curated molecular mechanism of the integrated nutrient signaling network in budding yeast, focusing on early temporal responses to carbon and nitrogen signaling. We build a computational model of this network to reconcile literature-curated quantitative experimental data with our proposed molecular mechanism. We evaluate the robustness of our estimates of the model’s kinetic parameter values. We test the model by comparing predictions made in mutant strains with qualitative experimental observations made in the same strains. Finally, we use the model to predict nutrient-responsive transcription factor activities in a number of mutant strains undergoing complex nutrient shifts. 

   more » « less
2. Dynamic cell cycle–dependent phosphorylation modulates CENP-L–CENP-N centromere recruitment

   https://doi.org/10.1091/mbc.E22-06-0239  

   Navarro, Alexandra P.; Cheeseman, Iain M. (September 2022, Molecular Biology of the Cell)

   Bloom, Kerry (Ed.)

   The kinetochore is a macromolecular structure that is needed to ensure proper chromosome segregation during each cellular division. The kinetochore is assembled upon a platform of the 16-subunit constitutive centromere-associated network (CCAN), which is present at centromeres throughout the cell cycle. The nature and regulation of CCAN assembly, interactions, and dynamics needed to facilitate changing centromere properties and requirements remain to be fully elucidated. The CENP-LN complex is a CCAN component that displays unique cell cycle–dependent localization behavior, peaking in the S phase. Here, we demonstrate that phosphorylation of CENP-L and CENP-N controls CENP-LN complex formation and localization in a cell cycle–dependent manner. Mimicking constitutive phosphorylation of either CENP-L or CENP-N or simultaneously preventing phosphorylation of both proteins prevents CENP-LN localization and disrupts chromosome segregation. Our work suggests that cycles of phosphorylation and dephosphorylation are critical for CENP-LN complex recruitment and dynamics at kinetochores to enable cell cycle–dependent CCAN reorganization. 

   more » « less
3. Potassium nutrient status drives posttranslational regulation of a low-K response network in Arabidopsis

   https://doi.org/10.1038/s41467-023-35906-5  

   Li, Kun-Lun; Tang, Ren-Jie; Wang, Chao; Luan, Sheng (December 2023, Nature Communications)

   Abstract Under low-potassium (K⁺) stress, a Ca²⁺signaling network consisting of calcineurin B-like proteins (CBLs) and CBL-interacting kinases (CIPKs) play essential roles. Specifically, the plasma membrane CBL1/9-CIPK pathway and the tonoplast CBL2/3-CIPK pathway promotes K⁺uptake and remobilization, respectively, by activating a series of K⁺channels. While the dual CBL-CIPK pathways enable plants to cope with low-K⁺stress, little is known about the early events that link external K⁺levels to the CBL-CIPK proteins. Here we show that K⁺status regulates the protein abundance and phosphorylation of the CBL-CIPK-channel modules. Further analysis revealed low K⁺-induced activation of VM-CBL2/3 happened earlier and was required for full activation of PM-CBL1/9 pathway. Moreover, we identified CIPK9/23 kinases to be responsible for phosphorylation of CBL1/9/2/3 in plant response to low-K⁺stress and the HAB1/ABI1/ABI2/PP2CA phosphatases to be responsible for CBL2/3-CIPK9 dephosphorylation upon K⁺-repletion. Further genetic analysis showed that HAB1/ABI1/ABI2/PP2CA phosphatases are negative regulators for plant growth under low-K⁺, countering the CBL-CIPK network in plant response and adaptation to low-K⁺stress. 

   more » « less
4. Integrated omics networks reveal the temporal signaling events of brassinosteroid response in Arabidopsis

   https://doi.org/10.1038/s41467-021-26165-3  

   Clark, Natalie M.; Nolan, Trevor M.; Wang, Ping; Song, Gaoyuan; Montes, Christian; Valentine, Conner T.; Guo, Hongqing; Sozzani, Rosangela; Yin, Yanhai; Walley, Justin W. (October 2021, Nature Communications)

   Abstract Brassinosteroids (BRs) are plant steroid hormones that regulate cell division and stress response. Here we use a systems biology approach to integrate multi-omic datasets and unravel the molecular signaling events of BR response inArabidopsis. We profile the levels of 26,669 transcripts, 9,533 protein groups, and 26,617 phosphorylation sites fromArabidopsisseedlings treated with brassinolide (BL) for six different lengths of time. We then construct a network inference pipeline called Spatiotemporal Clustering and Inference of Omics Networks (SC-ION) to integrate these data. We use our network predictions to identify putative phosphorylation sites on BES1 and experimentally validate their importance. Additionally, we identify BRONTOSAURUS (BRON) as a transcription factor that regulates cell division, and we show thatBRONexpression is modulated by BR-responsive kinases and transcription factors. This work demonstrates the power of integrative network analysis applied to multi-omic data and provides fundamental insights into the molecular signaling events occurring during BR response. 

   more » « less
5. Shining light on plant growth: recent insights into phytochrome-interacting factors

   https://doi.org/10.1093/jxb/erae276  

   Cai, Xingbo; Huq, Enamul; Panigrahy, ed., Madhusmita (June 2024, Journal of Experimental Botany)

   Abstract Light serves as a pivotal environmental cue regulating various aspects of plant growth and development, including seed germination, seedling de-etiolation, and shade avoidance. Within this regulatory framework, the basic helix–loop–helix transcription factors known as phytochrome-interacting factors (PIFs) play an essential role in orchestrating responses to light stimuli. Phytochromes, acting as red/far-red light receptors, initiate a cascade of events leading to the degradation of PIFs (except PIF7), thereby triggering transcriptional reprogramming to facilitate photomorphogenesis. Recent research has unveiled multiple post-translational modifications that regulate the abundance and/or activity of PIFs, including phosphorylation, dephosphorylation, ubiquitination, deubiquitination, and SUMOylation. Moreover, intriguing findings indicate that PIFs can influence chromatin modifications. These include modulation of histone 3 lysine 9 acetylation (H3K9ac), as well as occupancy of histone variants such as H2A.Z (associated with gene repression) and H3.3 (associated with gene activation), thereby intricately regulating downstream gene expression in response to environmental cues. This review summarizes recent advances in understanding the role of PIFs in regulating various signaling pathways, with a major focus on photomorphogenesis. 

   more » « less