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Nutrients are vital to life through intertwined sensing, signaling, and metabolic processes. Emerging research focuses on how distinct nutrient signaling networks integrate and coordinate gene expression, metabolism, growth, and survival. We review the multifaceted roles of sugars, nitrate, and phosphate as essential plant nutrients in controlling complex molecular and cellular mechanisms of dynamic signaling networks. Key advances in central sugar and energy signaling mechanisms mediated by the evolutionarily conserved master regulators HEXOKINASE1 (HXK1), TARGET OF RAPAMYCIN (TOR), and SNF1-RELATED PROTEIN KINASE1 (SNRK1) are discussed. Significant progress in primary nitrate sensing, calcium signaling, transcriptome analysis, and root-shoot communication to shape plant biomass and architecture are elaborated. Discoveries on intracellular and extracellular phosphate signaling and the intimate connections with nitrate and sugar signaling are examined. This review highlights the dynamic nutrient, energy, growth, and stress signaling networks that orchestrate systemwide transcriptional, translational, and metabolic reprogramming, modulate growth and developmental programs, and respond to environmental cues.
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Desenvolvimento Vegetal , Transdução de Sinais , Nutrientes , Desenvolvimento Vegetal/genética , Plantas/genética , Plantas/metabolismo , Transdução de Sinais/genéticaRESUMO
Plant roots explore the soil for water and nutrients, thereby determining plant fitness and agricultural yield, as well as determining ground substructure, water levels, and global carbon sequestration. The colonization of the soil requires investment of carbon and energy, but how sugar and energy signaling are integrated with root branching is unknown. Here, we show through combined genetic and chemical modulation of signaling pathways that the sugar small-molecule signal, trehalose-6-phosphate (T6P) regulates root branching through master kinases SNF1-related kinase-1 (SnRK1) and Target of Rapamycin (TOR) and with the involvement of the plant hormone auxin. Increase of T6P levels both via genetic targeting in lateral root (LR) founder cells and through light-activated release of the presignaling T6P-precursor reveals that T6P increases root branching through coordinated inhibition of SnRK1 and activation of TOR. Auxin, the master regulator of LR formation, impacts this T6P function by transcriptionally down-regulating the T6P-degrader trehalose phosphate phosphatase B in LR cells. Our results reveal a regulatory energy-balance network for LR formation that links the 'sugar signal' T6P to both SnRK1 and TOR downstream of auxin.
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Proteínas de Arabidopsis , Arabidopsis , Fosfatos Açúcares , Arabidopsis/genética , Trealose , Ácidos Indolacéticos , Proteínas Serina-Treonina Quinases/genética , Proteínas de Arabidopsis/genéticaRESUMO
Plants have evolved delicate systems for stimulating or inhibiting inorganic phosphate (Pi) uptake in response to the fluctuating Pi availability in soil. However, the negative regulators inhibiting Pi uptake at the transcriptional level are largely unexplored. Here, we functionally characterized a transcription factor in rice (Oryza sativa), OsWRKY10. OsWRKY10 encodes a nucleus-localized protein and showed preferential tissue localization. Knockout of OsWRKY10 led to increased Pi uptake and accumulation under Pi-replete conditions. In accordance with this phenotype, OsWRKY10 was transcriptionally induced by Pi, and a subset of PHOSPHATE TRANSPORTER 1 (PHT1) genes were up-regulated upon its mutation, suggesting that OsWRKY10 is a transcriptional repressor of Pi uptake. Moreover, rice plants expressing the OsWRKY10-VP16 fusion protein (a dominant transcriptional activator) accumulated even more Pi than oswrky10. Several lines of biochemical evidence demonstrated that OsWRKY10 directly suppressed OsPHT1;2 expression. Genetic analysis showed that OsPHT1;2 was responsible for the increased Pi accumulation in oswrky10. Furthermore, during Pi starvation, OsWRKY10 protein was degraded through the 26S proteasome. Altogether, the OsWRKY10-OsPHT1;2 module represents a crucial loop in the Pi signaling network in rice, inhibiting Pi uptake when there is ample Pi in the environment.
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Oryza , Oryza/genética , Oryza/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fosfatos/metabolismo , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Raízes de Plantas/metabolismoRESUMO
Tomato flower abscission is a critical agronomic problem directly affecting yield. It often occurs in greenhouses in winter, with the weak light or hazy weather leading to insufficient photosynthates. The importance of carbohydrate availability in flower retention has been illustrated, while relatively little is understood concerning the mechanism of carbohydrate regulation on flower abscission. In the present study, we analyzed the responding pattern of nonstructural carbohydrates (NSC, including total soluble sugars and starch) and the potential sugar signal pathway involved in abscission regulation in tomato flowers under shading condition, and their correlations with flower abscission rate and abscission-related hormones. The results showed that, when plants suffer from short-term photosynthesis deficiency, starch degradation in flower organs acts as a self-protection mechanism, providing a carbon source for flower growth and temporarily alleviating the impact on flower development. Trehalose 6-phosphate (T6P) and sucrose non-fermenting-like kinase (SnRK1) signaling seems to be involved in adapting the metabolism to sugar starvation stress through regulating starch remobilization and crosstalk with IAA, ABA, and ethylene in flowers. However, a continuous limitation of assimilating supply imposed starch depletion in flowers, which caused flower abscission.
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Carboidratos/genética , Flores/genética , Flores/fisiologia , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , Inanição/genética , Metabolismo dos Carboidratos/genética , Regulação da Expressão Gênica de Plantas/genética , Fotossíntese/genética , Reguladores de Crescimento de Plantas/genética , Transdução de Sinais/genética , Transcriptoma/genéticaRESUMO
Phosphorus (P) is an essential element for plant growth and development. Vacuoles play a fundamental role in the storage and remobilization of P in plants, while our understanding of the evolutionary mechanisms of creating and reusing P stores are limited. Besides, we also know very little about the coordination of intercellular P translocation, neither the inorganic phosphate (Pi) signaling nor the Pi transport patterns. Here we summarize recent advances in understanding the core elements involved in cellular and/or subcellular P homeostasis and signaling in unicellular green algae and multicellular land plants. We also propose further work that might help to uncover the high-resolution intracellular and intercellular landscape of Pi distribution and signaling in plants.
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Clorófitas , Embriófitas , Transporte Biológico , Fosfatos/metabolismo , Vacúolos/metabolismoRESUMO
Phosphate (Pi) is the plant-accessible form of phosphorus, and its insufficiency limits plant growth. The over-accumulation of anthocyanins in plants is often an indication of Pi starvation. However, whether the two pathways are directly linked and which components are involved in this process await identification. Here, we demonstrate that SPX4, a conserved regulator of the Pi response, transduces the Pi starvation signal to anthocyanin biosynthesis in Arabidopsis. When phr1spx4 plants were grown under low Pi conditions, DFR expression and anthocyanin biosynthesis were induced, which distinguished the plant from the behavior reported in the phr1 mutant. We also provide evidence that SPX4 interacts with PAP1, an MYB transcription factor that controls the anthocyanin biosynthetic pathway, in an inositol polyphosphate-dependent manner. Through a physical interaction, SPX4 prevented PAP1 from binding to its target gene promoter; by contrast, during Pi-deficient conditions, in the absence of inositol polyphosphates, PAP1 was released from SPX to activate anthocyanin biosynthesis. Our results reveal a direct link between Pi deficiency and flavonoid metabolism. This new regulatory module, at least partially independent from PHR1, may contribute to developing a strategy for plants to adapt to Pi starvation.
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Proteínas de Arabidopsis , Arabidopsis , Antocianinas , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas Associadas a Pancreatite , Fósforo , Fatores de Transcrição/genéticaRESUMO
The ability of an organism to maintain homeostasis in changing conditions is crucial for growth and survival. Eukaryotes have developed complex signaling pathways to adapt to a readily changing environment, including the inositol phosphate (InsP) signaling pathway. In plants and humans the pyrophosphorylated inositol molecules, inositol pyrophosphates (PP-InsPs), have been implicated in phosphate and energy sensing. PP-InsPs are synthesized from the phosphorylation of InsP6, the most abundant InsP. The plant PP-InsP synthesis pathway is similar but distinct from that of the human, which may reflect differences in how molecules such as Ins(1,4,5)P3 and InsP6 function in plants vs. animals. In addition, PP-InsPs can potentially interact with several major signaling proteins in plants, suggesting PP-InsPs play unique signaling roles via binding to protein partners. In this review, we will compare the biosynthesis and role of PP-InsPs in animals and plants, focusing on three central themes: InsP6 synthesis pathways, synthesis and regulation of the PP-InsPs, and function of a specific protein domain called the Syg1, Pho1, Xpr1 (SPX ) domain in binding PP-InsPs and regulating inorganic phosphate (Pi) sensing. This review will provide novel insights into the biosynthetic pathway and bioactivity of these key signaling molecules in plant and human systems.
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Inositol 1,4,5-Trifosfato/metabolismo , Ácido Fítico/metabolismo , Transdução de Sinais , Animais , Humanos , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Virais/metabolismo , Receptor do Retrovírus Politrópico e XenotrópicoRESUMO
Jasmonic acid (JA) biosynthesis and signaling are activated in Arabidopsis cultivated in phosphate (Pi) deprived conditions. This activation occurs mainly in photosynthetic tissues and is less important in roots. In leaves, the enhanced biosynthesis of JA coincides with membrane glycerolipid remodeling triggered by the lack of Pi. We addressed the possible role of JA on the dynamics and magnitude of glycerolipid remodeling in response to Pi deprivation and resupply. Based on combined analyses of gene expression, JA biosynthesis and glycerolipid remodeling in wild-type Arabidopsis and in the coi1-16 mutant, JA signaling seems important in the determination of the basal levels of phosphatidylcholine, phosphatidic acid (PA), monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol. JA impact on MGDG steady state level and fluctuations seem contradictory. In the coi1-16 mutant, the steady state level of MGDG is higher, possibly due to a higher level of PA in the mutant, activating MGD1, and to an increased expression of MGD3. These results support a possible impact of JA in limiting the overall content of this lipid. Concerning lipid variations, upon Pi deprivation, JA seems rather associated with a specific MGDG increase. Following Pi resupply, whereas the expression of glycerolipid remodeling genes returns to basal level, JA biosynthesis and signaling genes are still upregulated, likely due to a JA-induced positive feedback remaining active. Distinct impacts on enzymes synthesizing MGDG, that is, downregulating MGD3, possibly activating MGD1 expression and limiting the activation of MGD1 via PA, might allow JA playing a role in a sophisticated fine tuning of galactolipid variations.
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Arabidopsis/metabolismo , Ciclopentanos/metabolismo , Glicolipídeos/metabolismo , Oxilipinas/metabolismo , Fosfatos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Homeostase , Transdução de SinaisRESUMO
Synthetic matrices emulating the physicochemical properties of tissue-specific ECMs are being developed at a rapid pace to regulate stem cell fate. Biomaterials containing calcium phosphate (CaP) moieties have been shown to support osteogenic differentiation of stem and progenitor cells and bone tissue formation. By using a mineralized synthetic matrix mimicking a CaP-rich bone microenvironment, we examine a molecular mechanism through which CaP minerals induce osteogenesis of human mesenchymal stem cells with an emphasis on phosphate metabolism. Our studies show that extracellular phosphate uptake through solute carrier family 20 (phosphate transporter), member 1 (SLC20a1) supports osteogenic differentiation of human mesenchymal stem cells via adenosine, an ATP metabolite, which acts as an autocrine/paracrine signaling molecule through A2b adenosine receptor. Perturbation of SLC20a1 abrogates osteogenic differentiation by decreasing intramitochondrial phosphate and ATP synthesis. Collectively, this study offers the demonstration of a previously unknown mechanism for the beneficial role of CaP biomaterials in bone repair and the role of phosphate ions in bone physiology and regeneration. These findings also begin to shed light on the role of ATP metabolism in bone homeostasis, which may be exploited to treat bone metabolic diseases.
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Adenosina/metabolismo , Fosfatos de Cálcio/química , Regulação da Expressão Gênica , Células-Tronco/citologia , Trifosfato de Adenosina/metabolismo , Materiais Biocompatíveis/química , Osso e Ossos/metabolismo , Fosfatos de Cálcio/metabolismo , Diferenciação Celular , Células Cultivadas/citologia , Cromatografia Líquida de Alta Pressão , Homeostase , Humanos , Células-Tronco Mesenquimais/citologia , Osteogênese/fisiologia , Fenótipo , Fosfatos/metabolismo , RNA Interferente Pequeno/metabolismo , Receptor A2B de Adenosina/metabolismo , Regeneração , Transdução de Sinais , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismoRESUMO
Anthocyanin accumulation is acknowledged as a phenotypic indicator of phosphate (Pi) starvation. However, negative regulators of this process and their molecular mechanisms remain largely unexplored. In this study, we demonstrate that WRKY33 acts as a negative regulator of phosphorus-status-dependent anthocyanin biosynthesis. WRKY33 regulates the expression of the gene encoding dihydroflavonol 4-reductase (DFR), a rate-limiting enzyme in anthocyanin production, both directly and indirectly. WRKY33 binds directly to the DFR promoter to repress its expression and also interferes with the MBW complex through interacting with PAP1 to indirectly influence DFR transcriptional activation. Under -Pi conditions, PHR1 interacts with WRKY33, and the protein level of WRKY33 decreases; the repression of DFR expression by WRKY33 is thus attenuated, leading to anthocyanin accumulation in Arabidopsis. Further genetic and biochemical assays suggest that PHR1 is also involved in regulating factors that affect WRKY33 protein turnover. Taken together, our findings reveal that Pi starvation represses WRKY33, a repressor of anthocyanin biosynthesis, to finely tune anthocyanin biosynthesis. This "double-negative logic" regulation of phosphorus-status-dependent anthocyanin biosynthesis is required for the maintenance of plant metabolic homeostasis during acclimation to Pi starvation.
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Antocianinas , Regulação da Expressão Gênica de Plantas , Fosfatos , Fatores de Transcrição , Aclimatação , Oxirredutases do Álcool/metabolismo , Oxirredutases do Álcool/genética , Antocianinas/biossíntese , Antocianinas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fosfatos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Phosphate (Pi) is involved in numerous metabolic processes and plays a vital role in plant growth. Green plants have evolved intricate molecular bases of Pi signaling to maintain cellular Pi homeostasis. Here, we summarize recent advances in the molecular and structural bases of central Pi signaling and discuss pending questions.
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Fosfatos , Plantas , Fosfatos/metabolismo , Plantas/genética , Plantas/metabolismo , Homeostase , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Acid soils are characterized by deficiencies in essential nutrient elements, oftentimes phosphorus (P), along with toxicities of metal elements, such as aluminum (Al), manganese (Mn), and cadmium (Cd), each of which significantly limits crop production. In recent years, impressive progress has been made in revealing mechanisms underlying tolerance to high concentrations of Al, Mn, and Cd. Phosphorus is an essential nutrient element that can alleviate exposure to potentially toxic levels of Al, Mn, and Cd. In this review, recent advances in elucidating the genes responsible for the uptake, translocation, and redistribution of Al, Mn, and Cd in plants are first summarized, as are descriptions of the mechanisms conferring resistance to these toxicities. Then, literature highlights information on interactions of P nutrition with Al, Mn, and Cd toxicities, particularly possible mechanisms driving P alleviation of these toxicities, along with potential applications for crop improvement on acid soils. The roles of plant phosphate (Pi) signaling and associated gene regulatory networks relevant for coping with Al, Mn, and Cd toxicities, are also discussed. To develop varieties adapted to acid soils, future work needs to further decipher involved signaling pathways and key regulatory elements, including roles fulfilled by intracellular Pi signaling. The development of new strategies for remediation of acid soils should integrate the mechanisms of these interactions between limiting factors in acid soils.
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Fósforo , Solo , Fósforo/metabolismo , Cádmio/toxicidade , Cádmio/metabolismo , Rizosfera , Produtos Agrícolas , Manganês/metabolismo , Alumínio/toxicidadeRESUMO
Gut microbiota and their secreted metabolites have an influence on the initiation and progression of colon cancer. Probiotics are extensively perceived as a potential microbiota-modulation strategy to promote the health of the host, while the effectiveness of preventing colon cancer based on microbiota therapy has not been confirmed, and antitumor mechanisms influenced by microbiota and their metabolites with the intervention of probiotics remain to be further investigated. In vitro, Lactobacillus (JY300-8 and JMR-01) significantly inhibited the proliferation of CT26, HT29, and HCT116 cells. Moreover, we studied the prevention and therapy efficiency of Lactobacillus and its underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by Lactobacillus in colon cancer models in mice. We demonstrated that the pre-administration of Lactobacillus (JY300-8 and JMR-01) for 20 days before establishing tumor models resulted in an 86.21% reduction in tumor formation rate compared to tumor control group. Subsequently, continuous oral administration of living Lactobacillus significantly suppresses tumor growth, and tumor volumes decrease by 65.2%. Microbiome and metabolome analyses reveal that Lactobacillus suppresses colonic tumorigenesis and progression through the modulation of gut microbiota homeostasis and metabolites, including the down-regulation of secondary bile acids, sphingosine 1-phosphate (S1P), and pyrimidine metabolism, as well as the production of anticarcinogenic compounds in tumor-bearing mice. Additionally, metabolome analyses of Lactobacillus (JY300-8 and JMR-01) indicate that living Lactobacillus could reduce the relative abundance of alanine and L-serine to suppress tumor progression by regulating the tumor microenvironment, including down-regulation of pyrimidine metabolism and S1P signaling in cancer. These findings provide a potential prevention strategy and therapeutic target for colon cancer through the intervention of dietary Lactobacillus. IMPORTANCE The modulation of gut microbiota and metabolites has a significant influence on the progression of colon cancer. Our research indicated that the intervention of probiotics is a potentially feasible strategy for preventing colon cancer. We have also revealed the underlying antitumor mechanism through the alteration of gut microbiota and their metabolites, which could lead to broader biomedical impacts on the prevention and therapy of colon cancer with microbiota-based therapy regulated by probiotics.
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[This corrects the article DOI: 10.3389/fpls.2022.914648.].
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Genetic variation in phosphorus utilization efficiency (PUE) widely exists among wheat genotypes. However, the underlying mechanisms are still unclear. Two contrasting wheat genotypes, Heng4399 (H4399) and Tanmai98 (TM98), were screened out from 17 bread wheat genotypes based on shoot soluble phosphate (Pi) concentrations. The TM98 had a significantly higher PUE than the H4399, especially under Pi deficiency. The induction of genes in the PHR1-centered Pi signaling pathway was significantly higher in TM98 than in H4399. Collectively, through a label-free quantitative proteomic analysis, 2110 high-confidence proteins were identified in shoots of the two wheat genotypes. Among them, 244 and 133 proteins were differentially accumulated under Pi deficiency in H4399 and TM98, respectively. The abundance of proteins related to nitrogen and phosphorus metabolic processes, small molecule metabolic process, and carboxylic acid metabolic process weas significantly affected by Pi deficiency in the shoots of the two genotypes. The abundance of proteins in energy metabolism, especially photosynthesis, was decreased by Pi deficiency in the shoots of H4399. Inversely, the PUE-efficient genotype TM98 could maintain protein abundance in energy metabolism. Moreover, the proteins involved in pyruvate metabolism, glutathione metabolism, and sulfolipid biosynthesis were significantly accumulated in TM98, which probably contributed to its high PUE. SIGNIFICANCE: Improving the PUE of wheat is urgent and crucial for sustainable agriculture. Genetic variation among wheat genotypes provides materials for exploring the underlying mechanisms for high PUE. This study selected two wheat genotypes with contrasting PUE to reveal the differences in the physiological and proteomic responses to phosphate deficiency. The PUE-efficiency genotype TM98 greatly induced the expression of genes in the PHR1-centered Pi signaling pathway. Subsequently, the TM98 could maintain the abundance of proteins related to energy metabolism and enhance the abundance of proteins involved in pyruvate metabolism, glutathione metabolism, and sulfolipid biosynthesis to increase PUE under Pi deficiency. The differentially expressed genes or proteins between the genotypes with contrasting PUE would provide potential and basis for breeding wheat varieties with improved phosphorus use efficiency.
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Proteômica , Triticum , Triticum/metabolismo , Melhoramento Vegetal , Genótipo , Fósforo/metabolismo , Fosfatos/metabolismo , Glutationa/genética , Glutationa/metabolismo , Piruvatos/metabolismoRESUMO
Nowadays, because of the great benefit to human health, more and more efforts have been made to increase the production of alkaloids in Pinellia ternata (Thunb.) Breit. Phosphate (Pi) plays a critical role in plant growth and development, as well as secondary metabolism. However, its effect and regulation mechanism of Pi signaling on alkaloid biosynthesis call for further exploration. Here, we reported that Pi starvation could induce alkaloid accumulation in P. ternata. We cloned a cDNA sequence encoding PtPHR1 from P. ternata, which was further identified by nuclear localization, transcription activity, and binding ability to the PHR1-binding sequence. We found that the transformation of PtPHR1 into the Arabidopsis phr1 mutant (designated as PtPHR1OE/phr1) led to the rescue of the phenotype of the phr1 mutant to that of the wild-type, including the expression level of Pi starvation-induced genes and anthocyanin accumulation. The combination of these biochemical and genetic experiments indicated that PtPHR1 was intended to have a role similar to that of AtPHR1 in Pi signaling and metabolic responses. Interestingly, we found that Pi starvation also induced the production of benzoic acid, an intermediate in the biosynthetic pathway of phenylpropylamino alkaloids. Furthermore, this induction effect was impaired in the phr1 mutant but partly recovered in PtPHR1OE/phr1 plants. Together, our data suggest that Pi starvation promoted benzoic acid-derived alkaloid biosynthesis in P. ternata under the control of PtPHR1. Our finding that PtPHR1 is involved in the regulation of Pi signaling on alkaloid biosynthesis shows a direct link between the Pi nutrient supply and secondary metabolism.
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Phosphorus (P) is obtained by plants as phosphate (Pi) from the soil and low Pi levels affects plant growth and development. Adaptation to low Pi condition entails sensing internal and external Pi levels and translating those signals to molecular and morphophysiological changes in the plant. In this review, we present findings related to local and systemin Pi sensing with focus the molecular mechanisms behind root system architectural changes and the impact of hormones and epigenetic mechanisms affecting those changes. We also present some of the recent advances in the Pi sensing and signaling mechanisms focusing on inositol pyrophosphate InsP8 and its interaction with SPX domain proteins to regulate the activity of the central regulator of the Pi starvation response, PHR.
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Radiotherapy for head-and-neck cancers frequently causes long-term hypofunction of salivary glands that severely compromises quality of life and is difficult to treat. Here, we studied effects and mechanisms of Sphingosine-1-phosphate (S1P), a versatile signaling sphingolipid, in preventing irreversible dry mouth caused by radiotherapy. Mouse submandibular glands (SMGs) were irradiated with or without intra-SMG S1P pretreatment. The saliva flow rate was measured following pilocarpine stimulation. The expression of genes related to S1P signaling and radiation damage was examined by flow cytometry, immunohistochemistry, quantitative RT-PCR, Western blotting, and/or single-cell RNA-sequencing. S1P pretreatment ameliorated irradiation-induced salivary dysfunction in mice through a decrease in irradiation-induced oxidative stress and consequent apoptosis and cellular senescence, which is related to the enhancement of Nrf2-regulated anti-oxidative response. In mouse SMGs, endothelial cells and resident macrophages are the major cells capable of producing S1P and expressing the pro-regenerative S1P receptor S1pr1. Both mouse SMGs and human endothelial cells are protected from irradiation damage by S1P pretreatment, likely through the S1pr1/Akt/eNOS axis. Moreover, intra-SMG-injected S1P did not affect the growth and radiosensitivity of head-and-neck cancer in a mouse model. These data indicate that S1P signaling pathway is a promising target for alleviating irradiation-induced salivary gland hypofunction.
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Intracellular signaling is conserved in eukaryotes to allow for response to extracellular signals and to regulate development and cellular functions. In fungi, inositol phosphate signaling has been shown to be involved in growth, sexual reproduction, and metabolic adaptation. However, reports on mushroom-forming fungi are lacking so far. In Schizophyllum commune, an inositol monophosphatase has been found up-regulated during sexual development. The enzyme is crucial for inositol cycling, where it catalyzes the last step of inositol phosphate metabolism, restoring the inositol pool from the monophosphorylated inositol monophosphate. We overexpressed the gene in this model basidiomycete and verified its involvement in cell wall integrity and intracellular trafficking. Strong phenotypes in mushroom formation and cell metabolism were evidenced by proteome analyses. In addition, altered inositol signaling was shown to be involved in tolerance towards cesium and zinc, and increased metal tolerance towards cadmium, associated with induced expression of kinases and repression of phosphatases within the inositol cycle. The presence of the heavy metals Sr, Cs, Cd, and Zn lowered intracellular calcium levels. We could develop a model integrating inositol signaling in the known signal transduction pathways governed by Ras, G-protein coupled receptors, and cAMP, and elucidate their different roles in development.