Integration Of Signaling Research Articles

CO2 Levels Modulate Carbon Utilization, Energy Levels and Inositol Polyphosphate Profile in Chlorella.

Microalgae have a growing recognition of generating biomass and capturing carbon in the form of CO2. The genus Chlorella has especially attracted scientists' attention due to its versatility in algal mass cultivation systems and its potential in mitigating CO2. However, some aspects of how these green microorganisms respond to increasing concentrations of CO2 remain unclear. In this work, we analyzed Chlorella sorokiniana and Chlorella vulgaris cells under low and high CO2 levels. We monitored different processes related to carbon flux from photosynthetic capacity to carbon sinks. Our data indicate that high concentration of CO2 favors growth and photosynthetic capacity of the two Chlorella strains. Different metabolites related to the tricarboxylic acid cycle and ATP levels also increased under high CO2 concentrations in Chlorella sorokiniana, reaching up to two-fold compared to low CO2 conditions. The signaling molecules, inositol polyphosphates, that regulate photosynthetic capacity in green microalgae were also affected by the CO2 levels, showing a deep profile modification of the inositol polyphosphates that over-accumulated by up to 50% in high CO2 versus low CO2 conditions. InsP4 and InsP6 increased 3- and 0.8-fold, respectively, in Chlorella sorokiniana after being subjected to 5% CO2 condition. These data indicate that the availability of CO2 could control carbon flux from photosynthesis to carbon storage and impact cell signaling integration and energy levels in these green cells. The presented results support the importance of further investigating the connections between carbon assimilation and cell signaling by polyphosphate inositols in microalgae to optimize their biotechnological applications.

Specific deletion of Axin1 leads to activation of β-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice.

Axin1 is a key regulator of canonical Wnt signaling pathway. Roles of Axin1 in skeletal development and in disease occurrence have not been fully defined. Here, we report that Axin1 is essential for lower limb development. Specific deletion of Axin1 in limb mesenchymal cells leads to fibular hemimelia (FH)-like phenotype, associated with tarsal coalition. Further studies demonstrate that FH disease is associated with additional defects in Axin1 knockout (KO) mice, including decreased osteoclast formation and defects in angiogenesis. We then provide in vivo evidence showing that Axin1 controls limb development through both canonical β-catenin and BMP signaling pathways. We demonstrate that inhibition of β-catenin or BMP signaling could significantly reverse the FH phenotype in mice. Together, our findings reveal that integration of β-catenin and BMP signaling by Axin1 is required for lower limb development. Defect in Axin1 signaling could lead to the development of FH disease.

AP1/Fra1 confers resistance to MAPK cascade inhibition in pancreatic cancer

Targeting KRAS downstream signaling remains an important therapeutic approach in pancreatic cancer. We used primary pancreatic ductal epithelial cells and mouse models allowing the conditional expression of oncogenic KrasG12D, to investigate KRAS signaling integrators. We observed that the AP1 family member FRA1 is tightly linked to the KRAS signal and expressed in pre-malignant lesions and the basal-like subtype of pancreatic cancer. However, genetic-loss-of-function experiments revealed that FRA1 is dispensable for KrasG12D-induced pancreatic cancer development in mice. Using FRA1 gain- and loss-of-function models in an unbiased drug screen, we observed that FRA1 is a modulator of the responsiveness of pancreatic cancer to inhibitors of the RAF–MEK–ERK cascade. Mechanistically, context-dependent FRA1-associated adaptive rewiring of oncogenic ERK signaling was observed and correlated with sensitivity to inhibitors of canonical KRAS signaling. Furthermore, pharmacological-induced degradation of FRA1 synergizes with MEK inhibitors. Our studies establish FRA1 as a part of the molecular machinery controlling sensitivity to MAPK cascade inhibition allowing the development of mechanism-based therapies.

The medial preoptic area and acute cocaine's stimulant effects in rats: Potential influences of estradiol and biological sex

The medial preoptic area (mPOA) in the hypothalamus is an important integrator of neuroendocrine signaling and a key regulator of both natural and drug-induced reward. Although the mPOA modulates sex differences in other behaviors, whether it also modulates sex differences in cocaine response remains unclear. To help us better understand the mPOA's role in sex differences associated with cocaine response, we examined cocaine-induced changes in locomotion and neural activity in the mPOA of male and female rats. In addition, neural activity in the striatum, a brain area known to be involved in cocaine response, was examined for comparison purposes. Fos, the protein product of the immediate early gene c-fos, was used as the marker of neural activity. Locomotion chambers were used to measure behavior, radioimmunoassays and vaginal lavages were used to determine hormonal status, and immunohistochemical assays were used to quantify Fos. To account for the effects of gonadal hormones, rats were left gonadally intact and categorized as either ‘low-estradiol’ or ‘high-estradiol’ based on their hormonal status on test day. Results indicate that high-estradiol females experienced greater cocaine-induced mPOA Fos-immunoreactivity (Fos-ir) and displayed greater cocaine-induced locomotion than low estradiol females. Conversely, high-estradiol males experienced less cocaine-induced mPOA Fos-ir and displayed less cocaine-induced locomotion than low-estradiol males. Cocaine-induced Fos-ir in the mPOA also correlated with cocaine-induced Fos-ir in areas of the striatum already associated with cocaine response. These findings further support the mPOA's role in the endocrine-mediated response to cocaine. It also identifies the mPOA as a contributor to sex differences in cocaine response and potential differences in vulnerability to developing cocaine use disorders.

Integration of reactive oxygen species and nutrient signalling to shape root system architecture.

Yield losses due to nutrient deficiency are estimated as the primary cause of the yield gap worldwide. Understanding how plant roots perceive external nutrient status and elaborate morphological adaptations in response to it is necessary to develop reliable strategies to increase crop yield. In the last decade, reactive oxygen species (ROS) were shown to be key players of the mechanisms underlying root responses to nutrient limitation. ROS contribute in multiple ways to shape the root system in response to nutritional cues, both as direct effectors acting on cell wall architecture and as second messengers in signalling pathways. Here, we review the mutual interconnections existing between perception and signalling of the most common forms of the major macronutrients (nitrogen, phosphorus and potassium), and ROS in shaping plant root system architecture. We discuss recent advances in dissecting the integration of these elements and their impact on morphological traits of the root system, highlighting the functional ductility of ROS and enzymes implied in ROS metabolism, such as class III peroxidases.

Characterization of the Functional Interplay between the BRD7 and BRD9 Homologues in mSWI/SNF Complexes.

Bromodomains (BRDs) are a family of evolutionarily conserved domains that are the main readers of acetylated lysine (Kac) residues on proteins. Recently, numerous BRD-containing proteins have been proven essential for transcriptional regulation in numerous contexts. This is exemplified by the multi-subunit mSWI/SNF chromatin remodeling complexes, which incorporate up to 10 BRDs within five distinct subunits, allowing for extensive integration of Kac signaling to inform transcriptional regulation. As dysregulated transcription promotes oncogenesis, we sought to characterize how BRD-containing subunits contribute molecularly to mSWI/SNF functions. By combining genome editing, functional proteomics, and cellular biology, we found that loss of any single BRD-containing mSWI/SNF subunit altered but did not fully disrupt the various mSWI/SNF complexes. In addition, we report that the downregulation of BRD7 is common in invasive lobular carcinoma and modulates the interactome of its homologue, BRD9. We show that these alterations exacerbate sensitivities to inhibitors targeting epigenetic regulators─notably, inhibitors targeting the BRDs of non-mSWI/SNF proteins. Our results highlight the interconnections between distinct mSWI/SNF complexes and their far-reaching impacts on transcriptional regulation in human health and disease. The mass spectrometry data generated have been deposited to MassIVE and ProteomeXchange and assigned the identifiers MSV000089357, MSV000089362, and PXD033572.

SYK Inhibitors, Entospletinib and Lanraplenib, Show Potent Anti-Leukemic Activity in Combination with Targeted Agents

Introduction: Spleen tyrosine kinase (SYK) acts as a key integrator of cellular signaling from surface contact and receptor tyrosine kinase receptors containing an immunoreceptor tyrosine-based activation motif (ITAM). In acute myeloid leukemia (AML), SYK serves as a relay to an oncogenic transcriptional regulatory network (TRN) linked to NPM1, HOXA9, and MEIS1 helping to suppress myeloid progenitor maturation and promote proliferation. The selective, oral SYK inhibitor, entospletinib (ENTO), has demonstrated clinical activity in HOXA9/MEIS1-driven AML with acceptable tolerability when combined with intensive induction chemotherapy. A global phase 3 trial (AGILITY, NCT05020665) is currently underway, evaluating the combination of ENTO with intensive induction/consolidation chemotherapy in patients with treatment-naive NPM1-mutated (NPM1m) AML with measurable residual disease as the primary endpoint. Lanraplenib (LANRA) is a next-generation SYK inhibitor with similar potency, enhanced selectivity, and more favorable pharmacologic properties that is currently being evaluated in combination with gilteritinib in patients with relapsed or refractory (R/R) FLT3-mutated AML (NCT05028751). Results: ENTO exhibits anti-proliferative activity in NPM1m AML with associated HOXA9/MEIS1 dysregulation in ex vivo drug sensitivity studies. We hypothesized that SYK inhibition could synergize with other targeted therapies to enhance anti-leukemic activity at different nodes in this pathway. To address this hypothesis, the FLT3 internal tandem duplication/MLL-rearranged cell lines, MOLM13 and MV411, were treated with increasing doses of either LANRA or ENTO in combination with a small molecule MLL-Menin inhibitor (SNDX5613). Synergistic anti-proliferative effects were observed across a broad range of concentrations. No combinatorial or single-agent SNDX5613 activity was seen in the KASUMI-1 AML cell line, which lacks an MLL rearrangement. Phenotypic studies using flow cytometry were performed to assess the mechanistic response for SYK inhibition with LANRA in combination with SNDX5613. LANRA was found to increase the percentage of CD11b-positive cells and mean fluorescence intensity, while SNDX5613 led to a marked increase in CD14. In contrast to either single agent, the combination triggered early apoptosis and cell death, suggesting a more complete blockade of the HOXA9/MEIS1 transcriptional program through synergistic inhibition by orthogonal mechanisms. Furthermore, treatment of leukemic cells with either ENTO or LANRA inhibited SYK auto-phosphorylation in a dose-dependent manner. We also explored the potential for synergistic activity with gilteritinib (FLT3 inhibitor) and venetoclax (BCL2 inhibitor) using patient-derived AML isolates ex vivo based on the potential for SYK signaling cross talk with FLT3 itself and survival pathways. We found strong synergistic anti-proliferative activity for the combination of LANRA with either gilteritinib or venetoclax. Patient-derived xenograft (PDX) studies also demonstrated deeper reductions in leukemic burden in the peripheral blood, liver, and bone marrow after 28 days of treatment. Follow-up PDX studies assessing overall survival and pharmacodynamic activity are ongoing using an optimized dosing regimen and schedule. Summary/Conclusion: SYK is a promising therapeutic target for genetically defined subsets of AML. Two highly selective SYK inhibitors are currently undergoing clinical testing in different but complementary clinical settings. Given its central role as a modulator of leukemogenic signaling, SYK inhibition has the potential to synergize with other targeted therapies in AML. In preclinical studies, LANRA-mediated SYK inhibition shows compelling anti-proliferative and pro-apoptotic activity in combination with gilteritinib, venetoclax, and SNDX5613 in genetically defined subsets of AML.

Comprehensive Interactome Analysis for the Sole Adenylyl Cyclase Cyr1 of Candida albicans.

Cyr1, the sole adenylyl cyclase of the fungal pathogen Candida albicans, is a central component of the cAMP/protein kinase A signaling pathway that controls the yeast-to-hypha transition. Cyr1 is a multivalent sensor and integrator of various external and internal signals. To better understand how these signals are relayed to Cyr1 to regulate its activity, we sought to establish the interactome of Cyr1 by using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics to identify the proteins that coimmunoprecipitated with Cyr1. The method identified 36 proteins as candidates for authentic Cyr1-interacting partners, together with two known Cyr1-binding proteins, Cap1 and Act1. Fourteen identified proteins belonged to three functional groups, including actin regulation, cell wall components, and mitochondrial activities, that are known to play important roles in cell morphogenesis. To validate the proteomics data, we used biochemical and genetic methods to characterize two cell wall-related proteins, Mp65 and Sln1. First, coimmunoprecipitation confirmed their physical association with Cyr1. Second, deleting either MP65 or SLN1 resulted in severe defects in filamentation on serum plates. This study establishes the first Cyr1 interactome and uncovers a potential role for cell wall proteins in directly regulating Cyr1 activity to determine growth forms in C. albicans. IMPORTANCE A critical virulence trait of the human fungal pathogen Candida albicans is its ability to undergo the yeast-to-hypha transition in response to diverse environmental and cellular stimuli. Previous studies suggested that the sole adenylyl cyclase of C. albicans, Cyr1, is a multivalent signal sensor and integrator synthesizing cAMP to activate the downstream hypha-promoting events through the cAMP/protein kinase A pathway. To fully understand how Cyr1 senses and processes multiple stimuli to generate appropriate signal outputs, it was necessary to identify and characterize Cyr1-interacting partners. This study employed SILAC-based quantitative proteomic approaches and identified 36 Cyr1-associated proteins, many having functions associated with hyphal morphogenesis. Coimmunoprecipitation verified two cell surface proteins, Mp65 and Sln1. Furthermore, genetic and phenotypic analyses demonstrated the cAMP-dependent roles of these two proteins in determining hyphal growth. Our study establishes the first Cyr1 interactome and uncovers new Cyr1 regulators that mediate cell surface signals to influence the growth mode of C. albicans.

Hypothalamic integrity is necessary for sustained weight loss after bariatric surgery: A prospective, cross-sectional study

ObjectiveThe hypothalamus is the main integrator of peripheral and central signals in the control of energy homeostasis. Its functional relevance for the effectivity of bariatric surgery is not entirely elucidated. Studying the effects of bariatric surgery in patients with hypothalamic damage might provide insight. Summary background dataProspective study to analyze the effects of bariatric surgery in patients with hypothalamic obesity (HO) vs. matched patients with common obesity (CO) with and without bariatric surgery. Methods65 participants were included (HO-surgery: n = 8, HO-control: n = 10, CO-surgery: n = 12, CO-control: n = 12, Lean-control: n = 23). Body weight, levels of anorexic hormones, gut microbiota, as well as subjective well-being/health status, eating behavior, and brain activity (via functional MRI) were evaluated. ResultsPatients with HO lost significantly less weight after bariatric surgery than CO-participants (total body weight loss %: 5.5 % vs. 26.2 %, p = 0.0004). After a mixed meal, satiety and abdominal fullness tended to be lowest in HO-surgery and did not correlate with levels of GLP-1 or PYY. Levels of PYY (11,151 ± 1667 pmol/l/h vs. 8099 ± 1235 pmol/l/h, p = 0.028) and GLP-1 (20,975 ± 2893 pmol/l/h vs. 13,060 ± 2357 pmol/l/h, p = 0.009) were significantly higher in the HO-surgery vs. CO-surgery group. Abundance of Enterobacteriaceae and Streptococcus was increased in feces of HO and CO after bariatric surgery. Comparing HO patients with lean-controls revealed an increased activation in insula and cerebellum to viewing high-caloric foods in left insula and cerebellum in fMRI. ConclusionsHypothalamic integrity is necessary for the effectiveness of bariatric surgery in humans. Peripheral changes after bariatric surgery are not sufficient to induce satiety and long-term weight loss in patients with hypothalamic damage.

Correction for Puckett et al., "Integration of Apoptosis Signal-Regulating Kinase 1-Mediated Stress Signaling with the Akt/Protein Kinase B-IκB Kinase Cascade".

This article refers to:Integration of Apoptosis Signal-Regulating Kinase 1-Mediated Stress Signaling with the Akt/Protein Kinase B-IκB Kinase Cascade

Endothelial β-arrestins regulate mechanotransduction by the type II bone morphogenetic protein receptor in primary cilia.

Modulation of endothelial cell behavior and phenotype by hemodynamic forces involves many signaling components, including cell surface receptors, intracellular signaling intermediaries, transcription factors, and epigenetic elements. Many of the signaling mechanisms that underlie mechanotransduction by endothelial cells are inadequately defined. Here we sought to better understand how β-arrestins, intracellular proteins that regulate agonist-mediated desensitization and integration of signaling by transmembrane receptors, may be involved in the endothelial cell response to shear stress. We performed both in vitro studies with primary endothelial cells subjected to β-arrestin knockdown, and in vivo studies using mice with endothelial specific deletion of β-arrestin 1 and β-arrestin 2. We found that β-arrestins are localized to primary cilia in endothelial cells, which are present in subpopulations of endothelial cells in relatively low shear states. Recruitment of β-arrestins to cilia involved its interaction with IFT81, a component of the flagellar transport protein complex in the cilia. β-arrestin knockdown led to marked reduction in shear stress response, including induction of NOS3 expression. Within the cilia, β-arrestins were found to associate with the type II bone morphogenetic protein receptor (BMPR-II), whose disruption similarly led to an impaired endothelial shear response. β-arrestins also regulated Smad transcription factor phosphorylation by BMPR-II. Mice with endothelial specific deletion of β-arrestin 1 and β-arrestin 2 were found to have impaired retinal angiogenesis. In conclusion, we have identified a novel role for endothelial β-arrestins as key transducers of ciliary mechanotransduction that play a central role in shear signaling by BMPR-II and contribute to vascular development.

The global integrative network: integration of signaling and metabolic pathways

The crosstalk between signaling and metabolic pathways has been known to play key roles in human diseases and plant biological processes. The integration of signaling and metabolic pathways can provide an essential reference framework for crosstalk analysis. However, current databases use distinct structures to present signaling and metabolic pathways, which leads to the chaos in the integrated networks. Moreover, for the metabolic pathways, the metabolic enzymes and the reactions are disconnected by the current widely accepted layout of edges and nodes, which hinders the topological analysis of the integrated networks. Here, we propose a novel “meta-pathway” structure, which uses the uniformed structure to display the signaling and metabolic pathways, and resolves the difficulty in linking the metabolic enzymes to the reactions topologically. We compiled a comprehensive collection of global integrative networks (GINs) by merging the meta-pathways of 7077 species. We demonstrated the assembly of the signaling and metabolic pathways using the GINs of four species—human, mouse, Arabidopsis, and rice. Almost all of the nodes were assembled into one major network for each of the four species, which provided opportunities for robust crosstalk and topological analysis, and knowledge graph construction.

Ca2+-modulated photoactivatable imaging reveals neuron-astrocyte glutamatergic circuitries within the nucleus accumbens

Astrocytes are key elements of brain circuits that are involved in different aspects of the neuronal physiology relevant to brain functions. Although much effort is being made to understand how the biology of astrocytes affects brain circuits, astrocytic network heterogeneity and plasticity is still poorly defined. Here, we have combined structural and functional imaging of astrocyte activity recorded in mice using the Ca2+-modulated photoactivatable ratiometric integrator and specific optostimulation of glutamatergic pathways to map the functional neuron-astrocyte circuitries in the nucleus accumbens (NAc). We showed pathway-specific astrocytic responses induced by selective optostimulation of main inputs from the prefrontal cortex, basolateral amygdala, and ventral hippocampus. Furthermore, co-stimulation of glutamatergic pathways induced non-linear Ca2+-signaling integration, revealing integrative properties of NAc astrocytes. All these results demonstrate the existence of specific neuron-astrocyte circuits in the NAc, providing an insight to the understanding of how the NAc integrates information.

Rice protein phosphatase 1 regulatory subunits OsINH2 and OsINH3 participate actively in growth and adaptive responses under abscisic acid.

Rice (Oryza sativa L.), a worldwide staple food crop, is affected by various environmental stressors that ultimately reduce yield. However, diversified physiological and molecular responses enable it to cope with adverse factors. It includes the integration of numerous signaling in which protein phosphatase 1 (PP1) plays a pivotal role. Research on PP1 has been mostly limited to the PP1 catalytic subunit in numerous cellular progressions. Therefore, we focused on the role of PP1 regulatory subunits (PP1r), OsINH2 and OsINH3, homologs of AtINH2 and AtINH3 in Arabidopsis, in rice growth and stress adaptations. Our observations revealed that these are ubiquitously expressed regulatory subunits that interacted and colocalized with their counter partners, type 1 protein phosphatase (OsTOPPs) but could not change their subcellular localization. The mutation in OsINH2 and OsINH3 reduced pollen viability, thereby affected rice fertility. They were involved in abscisic acid (ABA)-mediated inhibition of seed germination, perhaps by interacting with osmotic stress/ABA-activated protein kinases (OsSAPKs). Meanwhile, they positively participated in osmotic adjustment by proline biosynthesis, detoxifying reactive oxygen species (ROS) through peroxidases (POD), reducing malondialdehyde formation (MDA), and regulating stress-responsive genes. Moreover, their co-interaction proposed they might mediate cellular processes together or by co-regulation; however, the special behavior of two different PP1r is needed to explore. In a nutshell, this research enlightened the involvement of OsINH2 and OsINH3 in the reproductive growth of rice and adaptive strategies under stress. Hence, their genetic interaction with ABA components and deep mechanisms underlying osmotic regulation and ROS adjustment would explain their role in complex signaling. This research offers the basis for introducing stress-resistant crops.

Envolvimento de auxinas no crescimento inicial de mudas de Impatiens walleriana cultivadas em bandejas

Abstract The key role of auxins as integrators of environmental signals has become well-known in recent years, and emerging evidence indicates that auxin biosynthesis is an essential component of the overall mechanisms of plant tolerance to stress. However, although the knowledge of the involvement auxins in the responses related to the generation of roots and accumulation of biomass, studies in ornamental species concerning the commercial propagation in plug cell trays are scarce. Thus, the aim of this work was to evaluate the accumulation of pre-transplant biomass in Impatiens walleriana plants growing in two propagation systems (soilless medium-based plug cell trays and a floating system) with trays of different cell sizes and sprayed either with a single dose of the auxin indole acetic acid (IAA) or with two inhibitors of endogenous auxins, N-1-naphthylphthalamic acid (NPA) and 2,3,5-triiodobenzoic acid (TIBA). Our results demonstrate that plants from both floating system and those sprayed with IAA present both the highest leaf area and fresh and dry weight at the end of the experiment. Conversely, as a negative control, the use of NPA and TIBA as antagonists of the synthesis and translocation of auxins caused an opposite effect in such variables as compared to control plants. However, before making commercial recommendations, it would be necessary to evaluate the potential post-transplant effects of these treatments on the generation of I. walleriana yield.

Developing a Microservices Integration Layer for Next-Generation Rail Operations Centers

This experience report provides insights into architectural challenges, design decisions, and lessons learned developing a microservices-based integration layer for Rail Operations Centre (ROC) systems. The discussed project is part of a Hitachi Rail R&D initiative to develop a modern solution that standardizes the integration of Hitachi Rail signaling and traffic management applications. We describe the system architecture, discuss the microservice API considerations, and share the lessons learned and the experiences operating a simplified implementation of the integration layer microservice API in the autonomous freight train project AutoHaul.

The Pro-Fibrotic Response to Lens Injury Is Signaled in a PI3K Isoform-Specific Manner.

The signaling inputs that function to integrate biochemical and mechanical cues from the extracellular environment to alter the wound-repair outcome to a fibrotic response remain poorly understood. Here, using a clinically relevant post-cataract surgery wound healing/fibrosis model, we investigated the role of Phosphoinositide-3-kinase (PI3K) class I isoforms as potential signaling integrators to promote the proliferation, emergence and persistence of collagen I-producing alpha smooth muscle actin (αSMA+) myofibroblasts that cause organ fibrosis. Using PI3K isoform specific small molecule inhibitors, our studies revealed a requisite role for PI3K p110α in signaling the CD44+ mesenchymal leader cell population that we previously identified as resident immune cells to produce and organize a fibronectin-EDA rich provisional matrix and transition to collagen I-producing αSMA+ myofibroblasts. While the PI3K effector Akt was alone insufficient to regulate myofibroblast differentiation, our studies revealed a role for Rac, another potential PI3K effector, in this process. Our studies further uncovered a critical role for PI3K p110α in signaling the proliferation of CD44+ leader cells, which is important to the emergence and expansion of myofibroblasts. Thus, these studies identify activation of PI3K p110α as a critical signaling input following wounding to the development and progression of fibrotic disease.

Integration of ABA, GA, and light signaling in seed germination through the regulation of ABI5

Seed germination is precisely controlled by a variety of signals, among which light signals and the phytohormones abscisic acid (ABA) and gibberellin (GA) play crucial roles. New findings have greatly increased our understanding of the mechanisms by which these three signals regulate seed germination and the close connections between them. Although much work has been devoted to ABA, GA, and light signal interactions, there is still no systematic description of their combination, especially in seed germination. In this review, we integrate ABA, GA, and light signaling in seed germination through the direct and indirect regulation of ABSCISIC ACID INSENSITIVE5 (ABI5), the core transcription factor that represses seed germination in ABA signaling, into our current understanding of the regulatory mechanism of seed germination.

The root apoplastic pH as an integrator of plant signaling.

Plant nutrition, growth, and response to environmental stresses are pH-dependent processes that are regulated at the apoplastic and subcellular levels. The root apoplastic pH is especially sensitive to external cues and can also be modified by intracellular inputs, such as hormonal signaling. Optimal crosstalk of the mechanisms involved in the extent and span of the apoplast pH fluctuations promotes plant resilience to detrimental biotic and abiotic factors. The fact that variations in local pHs are a standard mechanism in different signaling pathways indicates that the pH itself can be the pivotal element to provide a physiological context to plant cell regions, allowing a proportional reaction to different situations. This review brings a collective vision of the causes that initiate root apoplastic pHs variations, their interaction, and how they influence root response outcomes.

A glucose-target of rapamycin signaling axis integrates environmental history of heat stress through maintenance of transcription-associated epigenetic memory in Arabidopsis.

In nature, plants cope with adversity and have established strategies that recall past episodes and enable them to better cope with stress recurrences by establishing a 'stress memory'. Emerging evidence suggests that glucose (Glc) and target of rapamycin (TOR), central regulators of plant growth, have remarkable functions in stress adaptation. However, whether TOR modulates a stress memory response is so far unknown. Global transcriptome profiling identified that Glc, through TOR, regulates the expression of numerous genes involved in thermomemory. Priming of TOR overexpressors with mild heat showed better stress endurance, whereas TOR RNAi showed reduced thermomemory. This thermomemory is linked with histone methylation at specific sites of heat stress (HS) genes. TOR promotes long-term accumulation of H3K4me3 on thermomemory-associated gene promoters, even when transcription of those genes reverts to their basal level. Our results suggest that ARABIDOPSIS TRITHORAX 1 (ATX1), an H3K4 methyltransferase already shown to regulate H3K4me3 levels at the promoters of HS recovery genes, is a direct target of TOR signaling. The TOR-activating E2Fa binds to the promoter of ATX1 and regulates its expression, which ultimately regulates thermomemory. Collectively, our findings reveal a mechanistic framework in which Glc-TOR signaling determines the integration of stress and energy signaling to regulate thermomemory.