Stress Signaling In Plants Research Articles

The role of CDPKs in plant development, nutrient and stress signaling.

The second messenger calcium (Ca2+) is a ubiquitous intracellular signaling molecule found in eukaryotic cells. In plants, the multigene family of calcium-dependent protein kinases (CDPKs) plays an important role in regulating plant growth, development, and stress tolerance. CDPKs sense changes in intracellular Ca2+ concentration and translate them into phosphorylation events that initiate downstream signaling processes. Several functional and expression studies on different CDPKs and their encoding genes have confirmed their multifunctional role in stress. Here, we provide an overview of the signal transduction mechanisms and functional roles of CDPKs. This review includes details on the regulation of secondary metabolites, nutrient uptake, regulation of flower development, hormonal regulation, and biotic and abiotic stress responses.

The key clock component ZEITLUPE (ZTL) negatively regulates ABA signaling by degradation of CHLH in Arabidopsis.

Ubiquitination-mediated protein degradation plays important roles in ABA signal transduction and delivering responses to chloroplast stress signals in plants, but additional E3 ligases of protein ubiquitination remain to be identified to understand the complex signaling network. Here we reported that ZEITLUPE (ZTL), an F-box protein, negatively regulates abscisic acid (ABA) signaling during ABA-inhibited early seedling growth and ABA-induced stomatal closure in Arabidopsis thaliana. Using molecular biology and biochemistry approaches, we demonstrated that ZTL interacts with and ubiquitinates its substrate, CHLH/ABAR (Mg-chelatase H subunit/putative ABA receptor), to modulate CHLH stability via the 26S proteasome pathway. CHLH acts genetically downstream of ZTL in ABA and drought stress signaling. Interestingly, ABA conversely induces ZTL phosphorylation, and high levels of ABA also induce CHLH proteasomal degradation, implying that phosphorylated ZTL protein may enhance the affinity to CHLH, leading to the increased degradation of CHLH after ABA treatment. Taken together, our results revealed a possible mechanism of reciprocal regulation between ABA signaling and the circadian clock, which is thought to be essential for plant fitness and survival.

Evolution, gene expression, and protein‒protein interaction analyses identify candidate CBL-CIPK signalling networks implicated in stress responses to cold and bacterial infection in citrus

BackgroundCold is a major abiotic stress and Huanglongbing and citrus canker disease are two devastating bacterial diseases for citrus. The Ca2+-CBL-CIPK network is known to regulate different types of stress signalling in plants. How do CBL–CIPK signalling networks function in response to cold and infection by CLas or Xcc in citrus?ResultsEight calcineurin B-like proteins (CBLs) and seventeen CBL-interacting protein kinases (CIPKs) were identified from the cold-tolerant satsuma mandarin ‘Guijing2501’ (Citrus. unshiu) and CLas/Xcc-sensitive sweet orange (C. sinensis). Phylogenetic analysis revealed that both CBL and CIPK family members in citrus were classified into an ancient and a recent clade according to their conserved domain characteristics and/or intron/exon structures. Genome duplication analysis suggested that both tandem and segmental duplications contributed to the amplification of the CBL and CIPK gene families in citrus under intense purifying selection, and the duplication events only existed in the recent clades. Expression comparison of the duplicated gene pairs indicated that the duplicated CBL and CIPK genes underwent functional differentiation. Further expression analysis identified that CBL1, 5, 6, and 8 and CIPK2, 8, 12, 15, 16, and 17 were significantly regulated by multiple stresses, including cold, Xcc infection and/or CLas infection, in citrus, whereas CBL2/7 and CIPK1/4/5/11/13/14 were independently highly regulated by cold and CIPK3 was uniquely responsive to Xcc infection. The combination analyses of targeted Y2H assay and expression analysis revealed that CBL6-CIPK8 was the common signalling network in response to cold and Xcc infection, while CBL6/CBL8-CIPK14 was uniquely responsive to cold in citrus. Further stable transformation and cold tolerance assay indicated that overexpression of CuCIPK16 enhanced the cold tolerance of transgenic Arabidopsis with higher POD activity and lower MDA content.ConclusionsIn this study, evolution, gene expression and protein‒protein interaction analyses of citrus CBLs and CIPKs were comprehensively conducted over a genome-wide range. The results will facilitate future functional characterization of individual citrus CBLs and CIPKs under specific stresses and provide clues for the clarification of cold tolerance and disease susceptibility mechanisms in corresponding citrus cultivars.

β-Cyclocitral Does Not Contribute to Singlet Oxygen-Signalling in Algae, but May Down-Regulate Chlorophyll Synthesis.

Light stress signalling in algae and plants is partially orchestrated by singlet oxygen (1O2), a reactive oxygen species (ROS) that causes significant damage within the chloroplast, such as lipid peroxidation. In the vicinity of the photosystem II reaction centre, a major source of 1O2, are two β-carotene molecules that quench 1O2 to ground-state oxygen. 1O2 can oxidise β-carotene to release β-cyclocitral, which has emerged as a 1O2-mediated stress signal in the plant Arabidopsis thaliana. We investigated if β-cyclocitral can have similar retrograde signalling properties in the unicellular alga Chlamydomonas reinhardtii. Using RNA-Seq, we show that genes up-regulated in response to exogenous β-cyclocitral included CAROTENOID CLEAVAGE DIOXYGENASE 8 (CCD8), while down-regulated genes included those associated with porphyrin and chlorophyll anabolism, such as tetrapyrrole-binding protein (GUN4), magnesium chelatases (CHLI1, CHLI2, CHLD, CHLH1), light-dependent protochlorophyllide reductase (POR1), copper target 1 protein (CTH1), and coproporphyrinogen III oxidase (CPX1). Down-regulation of this pathway has also been shown in β-cyclocitral-treated A. thaliana, indicating conservation of this signalling mechanism in plants. However, in contrast to A. thaliana, a very limited overlap in differential gene expression was found in β-cyclocitral-treated and 1O2-treated C. reinhardtii. Furthermore, exogenous treatment with β-cyclocitral did not induce tolerance to 1O2. We conclude that while β-cyclocitral may down-regulate chlorophyll synthesis, it does not seem to contribute to 1O2-mediated high light stress signalling in algae.

Dodder-transmitted mobile systemic signals activate a salt-stress response characterized by a transcriptome change in Citrus sinensis.

Citrus is an essential horticultural fruit whose yield and quality are affected by salinity all over the world. The recognition and adaptive regulation of citrus against salt stress are important areas for cultivar improvement, but the vascular system signal transduction mechanism of the plant response to salt stress remains elusive. In this study, we constructed a dodder (Cuscuta spp.) linked Hamlin sweet orange (Citrus sinensis) plant community in which deliver a vascular signal through the dodder in response to salt stress. RNA-seq technology was used to analyze the gene expression profile of citrus leaves after salt treatment. The results showed that a vascular signal was transmitted to a dodder-linked host plant, triggering a transcriptional response to salt stress. However, the phenotypic and transudative ability of the dodder changed after 24 h. The salt treatment group (Group S) and the dodder-linked group (Group D) respectively contained 1,472 and 557 differentially expressed genes (DEGs). 454 of which were common to both groups. The results of our analysis revealed that the gene expression categories in Group D represented a highly consistent trend compared to the group S plants, indicating that the dodder-bridged vascular signals activated the stress-response of citrus leaves for transcriptomic reconfiguration. The KEGG pathway database and an analysis of key drivers revealed that phenylpropanoid biosynthesis, photosynthesis-antenna proteins, starch and sucrose metabolism, plant hormone signal transduction, circadian rhythm, and MAPK signaling pathways were significantly enriched as the critical genes during salt stress. A systemic signal in the dodder-bridged host significantly regulated abiotic stress-related secondary metabolic pathways, including those for phenylpropanoids, lignin, and lignans. The physiological indexes of photosynthetic intensity, respiration, and attractiveness among communities supported the transcriptional changes. Thus, our results indicate that salt stress-induced vascular system signals can be transmitted through the vascular system of a dodder linking citrus plants, revealing the genetic regulation and physiological changes of citrus leaves responding to plant stress signal transmission.

Phosphoproteome profiling of rice tissues provides new insights into responsive mechanisms and kinase activity upon salt stress

Rice is a model monocot plant and a major food crop worldwide that is known as the most salt-sensitive cereal. Phosphorylation of proteins regulates the stimulus perception and triggers responses; however, remains largely unknown in crops, particularly in rice under salinity. Here, we report in-depth physiological, proteomic, and phosphoproteomic kinetics of rice shoot and root tissues in response to short-term salt stress. We identified 8160 proteins, 5684 phosphopeptides that assigned to 3142 ‎phosphoproteins. In the root, hypophosphorylation of KAT1, BORs, HAKs, NHX2, and NHX8 transporters, RBOHs and nitrate reductase implied less efficiency in ion, minerals, and ROS haemostasis, thus likely resulting in membrane damages and sensitivity of rice to salinity. Predominantly, the PKA, CDK, MAPK, and PP2A families modulated plant response through interaction with densely interconnected protein modules. We identified 17 phosphomotifs reflecting the identities of the upstream kinases. Furthermore, phylogenetic mapping of 245 identified kinases together with the kinase of known target motifs and function, expanded the biological characters of kinases in rice. We also assigned target motifs for rice kinase families, including PDK1, PKA, CAMKL, CK1, CDK, GSK, and MAPK. This study expands the set of kinase substrates and their signaling networks. Our data also assigns new stress-responsive functions to a large number of novel phosphoproteins, thus will serve as a resource for further studies of salt stress signaling in plants. • We represent the largest profiling of 5422 phosphopeptides in rice upon salinity. • Critical transporters hypophosphorylated like KAT1, BORs, HAKs, NHX2/8, NCX1, CAX1. • CAMTA1/3/4, CDPK12/17/20/24, CBL23, RLKs, and PP2C likely caused salt sensitivity. • Phospho-regulation by PKA, CDK, MAPK, and PP2A families modulated plant response. • This study assigns stress-responsive functions to numerous novel phosphoproteins.

Abiotic stress signaling in plants and transgenic technology as a triumph: A review

Isolation and characterization of Soybean DREB 3 transcriptional activatorSarosha Nasreen, J. Amudha, S. S. Pandey

Sensing Mechanisms: Calcium Signaling Mediated Abiotic Stress in Plants.

Plants are exposed to various environmental stresses. The sensing of environmental cues and the transduction of stress signals into intracellular signaling are initial events in the cellular signaling network. As a second messenger, Ca2+ links environmental stimuli to different biological processes, such as growth, physiology, and sensing of and response to stress. An increase in intracellular calcium concentrations ([Ca2+]i) is a common event in most stress-induced signal transduction pathways. In recent years, significant progress has been made in research related to the early events of stress signaling in plants, particularly in the identification of primary stress sensors. This review highlights current advances that are beginning to elucidate the mechanisms by which abiotic environmental cues are sensed via Ca2+ signals. Additionally, this review discusses important questions about the integration of the sensing of multiple stress conditions and subsequent signaling responses that need to be addressed in the future.

Expression of a Pennisetum glaucum gene DREB2A confers enhanced heat, drought and salinity tolerance in transgenic Arabidopsis

Pearl millet (Pennisetum glaucum) is an essential cereal crop, whose growth and yield are not impacted by abiotic stresses, such as drought, heat, and cold. The DREB transcription factors (TF) are some of the largest groups of TFs in plants and play varied roles in plant stress response and signal transduction. In the present study, PgDREB2A gene encoding a DREB transcription factor in pearl millet was functionally characterized in Arabidopsis. DREB2A proteins contain a conserved domain that binds toethylene responsive element binding factors. Three different T1 transgenic lines overexpressing PgDREB2A gene were identified by Southern blot. Quantitative real-time polymerase chain reaction exhibited that PgDREB2A could be induced under drought conditions. As compared with the control, PgDREB2A overexpressing transgenic Arabidopsis showed increased rate of seed germination and root growth in transgenic lines under higher concentrations of mannitol, NaCl, ABA, heat and cold stress. Additionally, PgDREB2A transgenic lines showed enhanced durability after rehydration and tolerance to drought and salt stress was augmented with increased proline and reduced MDA build-up and diminishing water loss. Results from this study suggested that PgDREB2A as a transcription factor may improve endurance to various abiotic stresses and can be employed for developing crops tolerant to abiotic stresses.

SNF1-Related Protein Kinase 1 Activity Represses the Canonical Translational Machinery.

Protein biosynthesis is achieved through translation, which consumes enormous energy. Therefore, under conditions of limited energy supply, translation progress should be strictly coordinated. Sucrose non-fermenting kinase1 (SNF1)-related protein kinase 1 (SnRK1) is an evolutionarily conserved master regulator of cellular energy stress signaling in plants. Rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana) SnRK1 enhance hypoxia tolerance and induce the expression of stress-related genes. However, whether SnRK1 modulates protein synthesis in plants is unknown. In this study, using translational reporter constructs transfected in Arabidopsis protoplasts we showed that the expression of OsSnRK1A and AtSnRK1.1 decreases the abundance of canonical proteins without affecting their encoding transcript levels and protein stability. Moreover, the loading of total mRNAs and GFP mRNAs into the heavy polysome fraction which is normally translated was attenuated in transgenic Arabidopsis lines constitutively expressing OsSnRK1A or AtSnRK1.1. Taken together, these results suggest that OsSnRK1A and AtSnRK1.1 suppress protein translation to maintain energy homeostasis.

Strawberry FaSnRK1α Regulates Anaerobic Respiratory Metabolism under Waterlogging

Sucrose nonfermenting-1-related protein kinase 1 (SnRK1) is a central integrator of plant stress and energy starvation signalling pathways. We found that the FaSnRK1α-overexpression (OE) roots had a higher respiratory rate and tolerance to waterlogging than the FaSnRK1α-RNAi roots, suggesting that FaSnRK1α plays a positive role in the regulation of anaerobic respiration under waterlogging. FaSnRK1α upregulated the activity of anaerobic respiration-related enzymes including hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). FaSnRK1α also enhanced the ability to quench reactive oxygen species (ROS) by increasing antioxidant enzyme activities. We sequenced the transcriptomes of the roots of both wild-type (WT) and FaSnRK1α-RNAi plants, and the differentially expressed genes (DEGs) were clearly enriched in the defence response, response to biotic stimuli, and cellular carbohydrate metabolic process. In addition, 42 genes involved in glycolysis and 30 genes involved in pyruvate metabolism were significantly regulated in FaSnRK1α-RNAi roots. We analysed the transcript levels of two anoxia-related genes and three ERFVIIs, and the results showed that FaADH1, FaPDC1, FaHRE2 and FaRAP2.12 were upregulated in response to FaSnRK1α, indicating that FaSnRK1α may be involved in the ethylene signalling pathway to improve waterlogging tolerance. In conclusion, FaSnRK1α increases the expression of ERFVIIs and further activates anoxia response genes, thereby enhancing anaerobic respiration metabolism in response to low-oxygen conditions during waterlogging.

Salicylic acid and adenine nucleotides regulate the electron transport system and ROS production in plant mitochondria

Although mitochondria have a central role in energy transduction and reactive oxygen species (ROS) production, the regulatory mechanisms and their involvement in plant stress signaling are not fully established. The phytohormone salicylic acid (SA) is an important regulator of mitochondria-mediated ROS production and defense signaling. The role of SA and adenine nucleotides in the regulation of the mitochondrial succinate dehydrogenase (SDH) complex activity and ROS production was analyzed using WT, RNAi SDH1‐1 and disrupted stress response 1 (dsr1) mutants, which show a point mutation in SDH1 subunit and are defective in SA signaling. Our results showed that SA and adenine nucleotides regulate SDH complex activity by distinct patterns, contributing to increased SDH-derived ROS production. As previously demonstrated, SA induces the succinate-quinone reductase activity of SDH complex, acting at or near the ubiquinone binding site. On the other hand, here we demonstrated that adenine nucleotides, such as AMP, ADP and ATP, induce the SDH activity provided by the SDH1 subunit. The regulation of SDH activity by adenine nucleotides is dependent on mitochondrial integrity and is prevented by atractyloside, an inhibitor of adenine nucleotide translocator (ANT), suggesting that the regulatory mechanism occurs on the mitochondrial matrix side of the inner mitochondrial membrane, and not in the intermembrane space, as previously suggested. On the other hand, in the intermembrane space, ADP and ATP limit mitochondrial oxygen consumption by a mechanism that appears to be related to cytochrome bc1 complex inhibition. Altogether, these results indicate that SA signaling and adenine nucleotides regulate the mitochondrial electron transport system and mitochondria-derived ROS production by direct effect in the electron transport system complexes, bringing new insights into mechanisms with direct implications in plant development and responses to different environmental responses, serving as a starting point for future physiological explorations.

Plant Salinity Sensors: Current Understanding and Future Directions.

Salt stress is a major limiting factor for plant growth and crop yield. High salinity causes osmotic stress followed by ionic stress, both of which disturb plant growth and metabolism. Understanding how plants perceive salt stress will help efforts to improve salt tolerance and ameliorate the effect of salt stress on crop growth. Various sensors and receptors in plants recognize osmotic and ionic stresses and initiate signal transduction and adaptation responses. In the past decade, much progress has been made in identifying the sensors involved in salt stress. Here, we review current knowledge of osmotic sensors and Na+ sensors and their signal transduction pathways, focusing on plant roots under salt stress. Based on bioinformatic analyses, we also discuss possible structures and mechanisms of the candidate sensors. With the rapid decline of arable land, studies on salt-stress sensors and receptors in plants are critical for the future of sustainable agriculture in saline soils. These studies also broadly inform our overall understanding of stress signaling in plants.

Cytosolic and Nucleosolic Calcium-Regulated Molecular Networks in Response to Long-Term Treatment with Abscisic Acid and Methyl Jasmonate in Arabidopsis thaliana.

Calcium acts as a universal secondary messenger that transfers developmental cues and stress signals for gene expression and adaptive growth. A prior study showed that abiotic stresses induce mutually independent cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic Ca2+ ([Ca2+]nuc) increases in Arabidopsis thaliana root cells. However, gene expression networks deciphering [Ca2+]cyt and [Ca2+]nuc signalling pathways remain elusive. Here, using transgenic A. thaliana to selectively impair abscisic acid (ABA)- or methyl jasmonate (MeJA)-induced [Ca2+]cyt and [Ca2+]nuc increases, we identified [Ca2+]cyt- and [Ca2+]nuc-regulated ABA- or MeJA-responsive genes with a genome oligo-array. Gene co-expression network analysis revealed four Ca2+ signal-decoding genes, CAM1, CIPK8, GAD1, and CPN20, as hub genes co-expressed with Ca2+-regulated hormone-responsive genes and hormone signalling genes. Luciferase complementation imaging assays showed interactions among CAM1, CIPK8, and GAD1; they also showed interactions with several proteins encoded by Ca2+-regulated hormone-responsive genes. Furthermore, CAM1 and CIPK8 were required for MeJA-induced stomatal closure; they were associated with ABA-inhibited seed germination. Quantitative reverse transcription polymerase chain reaction analysis showed the unique expression pattern of [Ca2+]-regulated hormone-responsive genes in cam1, cipk8, and gad1. This comprehensive understanding of distinct Ca2+ and hormonal signalling will allow the application of approaches to uncover novel molecular foundations for responses to developmental and stress signals in plants.

The potential role of plasma membrane proteins in response to Zn stress in rice roots based on iTRAQ and PRM under low Cd condition

Cd pollution had already caused serious threats to crop growth and development, food safety and human health, and become a potential agricultural and global environmental problem. Zn had been used to reduce Cd accumulation in soil and plants. Proteins located in plasma membrane (PM) played important roles in transferring stress signals in plants. To further elucidate how PM proteins modulated Zn/Cd transport under low-Cd condition, quantitative proteomics was employed to identify and verify the differentially expressed proteins (DEPs) and their biological functions at proteome level. A total of 4008 proteins were identified, and 332 DEPs (192 up and 140 down, fold >1.50 or <0.66, p < 0.01) were screened. Functional analysis showed that DEPs were mainly catalytic active and binding proteins, involved in glutathione metabolism, phenylpropanoid biosynthesis, etc. DEPs involved in ion transport played key roles in regulating transmembrane transport, resisting stress and alleviating toxicity of heavy metals to rice roots. DEPs were as the marker proteins in rice root responding to heavy metal stress. This study had important guiding significances for metal ions transport mechanism and screening of biomarkers responding to abiotic stress, and provided references for further researches underlying abiotic stress and detoxication in rice and other plants.

Affinity Purification Followed by Liquid Chromatography-Tandem Mass Spectrometry to Identify Proteins Interacting with ABA Signaling Components.

Abscisic acid (ABA) is a key phytohormone involved in plant development, seed germination and responses to osmotic stresses, such as drought and high salinity. SNF1-related protein kinases (SnRK2s) play important roles in ABA-dependent and ABA-independent osmotic stress signaling. SnRK2s phosphorylate transcription factors and ion channels in response to ABA or osmotic stress to induce the expression of stress-responsive genes and stomatal closure, respectively, to confer osmotic stress tolerance. The activity of SnRK2s is directly or indirectly regulated by several protein factors. Identification of downstream substrates or upstream regulators of SnRK2s is very useful for elucidating protein components that regulate ABA and osmotic stress signaling. Here, we describe the use of affinity purification by coimmunoprecipitation and liquid chromatography-tandem mass spectrometry to identify protein complexes involved in ABA and osmotic stress signaling in plants. We previously identified several protein factors that regulate ABA and osmotic stress signaling by using this method.

Exosome mediated cell signal toward breast cancer metastasis: A comprehensive review

Abiotic stress signaling in plants and transgenic technology as a triumph: A reviewSeetha Babu Manepalli, Shraddha Tomar, Dinkar J. Gaikwad, Sagar Maitra

Leucine-rich repeat receptor-like protein kinase AtORPK1 promotes oxidative stress resistance in an AtORPK1-AtKAPP mediated module in Arabidopsis

Signal perception and transduction by the cell surface receptors are essential for cell-cell communication and plant response to abiotic stress. In this work, a previously uncharacterized leucine-rich repeat receptor-like kinase (LRR-RLK), Oxidative-stress Related Protein Kinase 1 (AtORPK1), was isolated from Arabidopsis thaliana, and its biological function was investigated in protoplasts, BY-2 cells and transgenic Arabidopsis plants. AtORPK1 is ubiquitously expressed in various tissues and organs of Arabidopsis at different developmental stages. Loss-of-function of AtORPK1 reduced, whereas overexpression of AtORPK1 increased, the oxidative stress resistance and oxidative stress responsive gene expression in orpk1 mutant and AtORPK1 transgenic Arabidopsis. Sub-cellular localization analyses revealed that AtORPK1 is localized to plasma membrane and endosomes, and the specific localization was significantly affected by hydrogen peroxide (H2O2) treatment. Further GFP, CFP, YFP and RFP fusion protein co-localization and FRET analyses demonstrated that AtORPK1 interacted and co-localized with AtKAPP, a common downstream phosphatase, in the enlarged endosomes such as prevacuolar compartments. Our results indicate that AtORPK1 functions as a positive molecular link between the oxidative stress signaling and antioxidant stress in plants.

Enhancement of drought tolerance in rice by silencing of the OsSYT-5 gene.

Improvement of drought tolerance of crops is a great challenge in conditions of increasing climate change. This report describes that the silencing of the synaptotagmin-5 (OsSYT-5) gene encoding the rice Ca2+ sensing protein with a C2 domain led to a significant improvement of rice tolerance to water deficit stress. Transgenic lines with suppressed expression of the OsSYT-5 gene exhibited an enhanced photosynthetic rate but reduced stomatal conductance and transpiration during water deficit stress. The abscisic acid (ABA) content under both normal and drought conditions was elevated in the leaves of the transgenic rice as compared to the wild type. The silencing of the OsSYT-5 gene affected the expression of several genes associated with ABA-related stress signaling in the transgenic rice plants. In the water deficit experiment, the transgenic lines with a silenced OsSYT-5 gene exhibited symptoms of drought stress seven days later than the wild type. Transgenic lines with suppressed OsSYT-5 gene expression exhibited higher pollen viability and produced more grains compared to the wild type at both normal and drought stress conditions.

Cross-Talks Between Macro- and Micronutrient Uptake and Signaling in Plants.

In nature, land plants as sessile organisms are faced with multiple nutrient stresses that often occur simultaneously in soil. Nitrogen (N), phosphorus (P), sulfur (S), zinc (Zn), and iron (Fe) are five of the essential nutrients that affect plant growth and health. Although these minerals are relatively inaccessible to plants due to their low solubility and relative immobilization, plants have adopted coping mechanisms for survival under multiple nutrient stress conditions. The double interactions between N, Pi, S, Zn, and Fe have long been recognized in plants at the physiological level. However, the molecular mechanisms and signaling pathways underlying these cross-talks in plants remain poorly understood. This review preliminarily examined recent progress and current knowledge of the biochemical and physiological interactions between macro- and micro-mineral nutrients in plants and aimed to focus on the cross-talks between N, Pi, S, Zn, and Fe uptake and homeostasis in plants. More importantly, we further reviewed current studies on the molecular mechanisms underlying the cross-talks between N, Pi, S, Zn, and Fe homeostasis to better understand how these nutrient interactions affect the mineral uptake and signaling in plants. This review serves as a basis for further studies on multiple nutrient stress signaling in plants. Overall, the development of an integrative study of multiple nutrient signaling cross-talks in plants will be of important biological significance and crucial to sustainable agriculture.