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Lysosomes play a pivotal role in coordinating macromolecule degradation and regulating cell growth and metabolism. Despite substantial progress in identifying lysosomal signaling proteins, understanding the pathways that synchronize lysosome functions with changing cellular demands remains incomplete. This study uncovers a role for TANK-binding kinase 1 (TBK1), well known for its role in innate immunity and organelle quality control, in modulating lysosomal responsiveness to nutrients. Specifically, we identify a pool of TBK1 that is recruited to lysosomes in response to elevated amino acid levels. This lysosomal TBK1 phosphorylates Rab7 on serine 72. This is critical for alleviating Rab7-mediated inhibition of amino acid-dependent mTORC1 activation. Furthermore, a TBK1 mutant (E696K) associated with amyotrophic lateral sclerosis and frontotemporal dementia constitutively accumulates at lysosomes, resulting in elevated Rab7 phosphorylation and increased mTORC1 activation. This data establishes the lysosome as a site of amino acid regulated TBK1 signaling that is crucial for efficient mTORC1 activation. This lysosomal pool of TBK1 has broader implications for lysosome homeostasis, and its dysregulation could contribute to the pathogenesis of ALS-FTD. Synopsis: In addition to their degradative functions, lysosomes play an important role in coordinating cellular responses to changes in nutrient availability. This study reveals that TBK1 is recruited to lysosomes when amino acids are abundant where it phosphorylates Rab7 and thus relieves Rab7-dependent suppression of mTORC1 signaling from lysosomes. TBK1 is recruited to lysosomes when amino acids are abundant. Rab7 (serine 72) is a substrate of TBK1 at lysosomes. Rab7 suppresses mTORC1 activity and this is relieved by TBK1-dependent phosphorylation of Rab7 on serine 72. The ALS-FTD associated E696K TBK1 mutant accumulates at lysosomes resulting in increased Rab7 phosphorylation and mTORC1 activity. TBK1 promotes mTORC1 activation by amino acids at the lysosome surface. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes that localize to the lysosomal surface through an unknown mechanism(s). Here, we show that mTORC1 is completely insensitive to amino acids in cells lacking the Rag GTPases or the Ragulator component p18. Moreover, not only are the Rag GTPases and Ragulator required for amino acids to regulate mTORC1, they are also essential for the lysosomal recruitment of the GATOR1, GATOR2, and KICSTOR complexes, which stably associate and traffic to the lysosome as the "GATOR" supercomplex. The nucleotide state of RagA/B controls the lysosomal association of GATOR, in a fashion competitively antagonized by the N terminus of the amino acid transporter SLC38A9. Targeting of Ragulator to the surface of mitochondria is sufficient to relocalize the Rags and GATOR to this organelle, but not to enable the nutrient-regulated recruitment of mTORC1 to mitochondria. Thus, our results reveal that the Rag-Ragulator complex is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway and underscore that mTORC1 activation requires signal transduction on the lysosomal surface. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a lethal disease with limited effective treatments. A deeper understanding of its molecular mechanisms is crucial to reduce incidence and mortality. Epidemiological evidence suggests a link between diet and disease risk, though dietary recommendations for at‐risk individuals remain debated. Here, we propose that cell‐intrinsic nutrient sensing pathways respond to specific diet‐derived cues to facilitate oncogenic transformation of pancreatic epithelial cells. This review explores how diet influences pancreatic cancer predisposition through nutrient sensing and downstream consequences for (pre‐)cancer cell biology. We also examine experimental evidence connecting specific food intake to pancreatic cancer progression, highlighting nutrient sensing as a promising target for therapeutic development to mitigate disease risk. [ABSTRACT FROM AUTHOR]

The luminal environment is rich in macronutrients coming from our diet and resident microbial populations including their metabolites. Together, they have the capacity to modulate unique cell surface receptors, known as G‐protein coupled receptors (GPCRs). Along the entire length of the gut epithelium, enteroendocrine cells express GPCRs to interact with luminal contents, such as GPR93 and the calcium sensing receptor to sense proteins, FFA2 and GPR84 to sense fatty acids, and SGLT1 and T1R to sense carbohydrates. Nutrient–receptor interaction causes the release of hormonal stores such as glucagon‐like peptide 1, peptide YY, and cholecystokinin, which further regulate gut function. Existing data show the role of luminal components and microbial fermentation products on gut function. However, there is a lack of understanding in the mechanistic interactions between diet‐derived luminal components and microbial products and nutrient‐sensing receptors and downstream gastrointestinal modulation. This review summarizes current knowledge on various luminal components and describes in detail the range of nutrients and metabolites and their interaction with nutrient receptors in the gut epithelium and the emerging impact on immune cells. [ABSTRACT FROM AUTHOR]

mTORC1 senses nutrients and growth factors and phosphorylates downstream targets, including the transcription factor TFEB, to coordinate metabolic supply and demand. These functions position mTORC1 as a central controller of cellular homeostasis, but the behavior of this system in individual cells has not been well characterized. Here, we provide measurements necessary to refine quantitative models for mTORC1 as a metabolic controller. We developed a series of fluorescent protein-TFEB fusions and a multiplexed immunofluorescence approach to investigate how combinations of stimuli jointly regulate mTORC1 signaling at the single-cell level. Live imaging of individual MCF10A cells confirmed that mTORC1-TFEB signaling responds continuously to individual, sequential, or simultaneous treatment with amino acids and the growth factor insulin. Under physiologically relevant concentrations of amino acids, we observe correlated fluctuations in TFEB, AMPK, and AKT signaling that indicate continuous activity adjustments to nutrient availability. Using partial least squares regression modeling, we show that these continuous gradations are connected to protein synthesis rate via a distributed network of mTORC1 effectors, providing quantitative support for the qualitative model of mTORC1 as a homeostatic controller and clarifying its functional behavior within individual cells.

Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery. Databases searched included Medline, Embase, Emcare, APA PsychInfo, Cochrane Library, and CINAHL. Two human and 21 animal studies were included. Bariatric surgery alters the quantity of many sweet, umami, and fatty acid taste receptors in the gastrointestinal tract. Changes to the expression of sweet and amino acid receptors occur most often in intestinal segments surgically repositioned more proximally, such as the alimentary limb after gastric bypass. Conversely, changes to fatty acid receptors were observed more frequently in the colon than in the small intestine. Significant heterogeneity in the methodology of included studies limited conclusions regarding the direction of change in taste receptor expression induced by bariatric surgeries. Few studies have investigated associations between taste receptor expression and clinical outcomes of bariatric surgery. As such, future studies should look to investigate the relationship between bariatric surgery-induced changes to gut taste receptor expression and function and the impact of surgery on taste preferences, food palatability, and eating behaviour. Registration code in PROSPERO: CRD42022313992 [ABSTRACT FROM AUTHOR]

Heterotrimeric GTP-binding proteins or G-proteins are pivotal players in the intricate signaling cascades of plant cells, operating through their binding to guanine nucleotides. These G-proteins primarily consist of three essential subunits: Gα, Gβ, and Gγ. Among these subunits, Gγ stands out for its remarkable genetic diversity. In the present investigation, six Gγ subunits were identified in the Indian variety T-163 of the pea plant (Pisum sativum). Notably, two of these novel Gγ subunits, named PsGγ1 and PsGγ2, belong to type A, while PsGγ3 falls within the type B category. The remaining three subunits, namely PsGγ4, PsGγ5, and PsGγ6, are classified under type C. An in-depth comparison of the amino acid sequences of these pea Gγ subunits with their counterparts in other plants, including Arabidopsis thaliana and Oryza sativa, has unveiled significant variations. This research explores the impact of different treatments on PsGγ genes (PsGγ1 to PsGγ6) in plants. Noteworthy discoveries include a 4-fold increase in the expression of PsGγ1, PsGγ4, PsGγ5, and PsGγ6 in the presence of nitrogen. PsGγ2 and PsGγ3, however, show no response. Phosphorus induces a 3-fold upregulation in PsGγ2 and PsGγ4, and a 4-fold increase in PsGγ5. Conversely, the absence of phosphorus triggers a 4-fold upregulation in PsGγ4 and PsGγ5. Heat stress leads to a 3-fold upregulation in PsGγ2, PsGγ4, and PsGγ5, while cold stress results in a 3-fold upregulation of PsGγ1 and PsGγ6. Under high salt conditions, PsGγ1, PsGγ3, PsGγ4, and PsGγ6 exhibit a 4-fold upregulation, with PsGγ2 showing a 2-fold increase. PsGγ4 and PsGγ5 display a 4-fold upregulation in response to ABA, while PsGγ2 and PsGγ3 show a 3-fold increase while MeJA induces a 4-fold upregulation in PsGγ5. Notably, this study unveils, for the first time, the significant role of Gγ subunits during endosymbiotic associations with phosphorus-acquiring AMF with AMF triggering a 4-fold upregulation in PsGγ4 and PsGγ6. The presence of multiple Gγ subunits in pea underscores their critical participation in governing plant development, stress responses, nutrient sensing, and interactions with mycorrhizal fungi.

Background: Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. Scope of Review: In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. Major Conclusions: Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily.

Abstract The luminal environment is rich in macronutrients coming from our diet and resident microbial populations including their metabolites. Together, they have the capacity to modulate unique cell surface receptors, known as G‐protein coupled receptors (GPCRs). Along the entire length of the gut epithelium, enteroendocrine cells express GPCRs to interact with luminal contents, such as GPR93 and the calcium sensing receptor to sense proteins, FFA2 and GPR84 to sense fatty acids, and SGLT1 and T1R to sense carbohydrates. Nutrient–receptor interaction causes the release of hormonal stores such as glucagon‐like peptide 1, peptide YY, and cholecystokinin, which further regulate gut function. Existing data show the role of luminal components and microbial fermentation products on gut function. However, there is a lack of understanding in the mechanistic interactions between diet‐derived luminal components and microbial products and nutrient‐sensing receptors and downstream gastrointestinal modulation. This review summarizes current knowledge on various luminal components and describes in detail the range of nutrients and metabolites and their interaction with nutrient receptors in the gut epithelium and the emerging impact on immune cells.

The central nervous system (CNS) relies on myelin for proper functioning. Myelin remodeling is a risk factor for neurometabolic and endocrine malfunction, resulting in cognitive decline and heightened susceptibility to neurological diseases. The plasticity of myelin upon nutrient shifts may lead to dietary and hormonal interventions for preventing and treating neural complications. [ABSTRACT FROM AUTHOR]

Increased anthropogenic emissions of carbon dioxide (CO2) have resulted in ocean acidification (OA) that is intertwined with enhanced ocean stratification. Diatoms are assumed to suffer from a more nutrient-limited condition in the future ocean. This study aimed to explore how OA affects the diatom dynamics under nutrient-poor conditions and the ability of diatoms to perceive nutrients (nitrogen, phosphorus, silicon, and trace metals) and cadmium (Cd) stimuli and assimilate nitrogen when receiving nutrients or Cd supplementation. Our study observed that diatom population grown under OA condition declined faster than those grown under ambient condition. Ocean acidification greatly lower intracellular Ca2+ concentration in diatom cells. Intracellular Ca2+ burst was involved in phosphorus accumulation but not in nitrogen, silicon, essential metals, and cadmium uptake. Our data demonstrate slower NO3– assimilation rates of diatoms grown in acidified seawater. Our study also indicates that diatoms have a poor perception of phosphorus availability under OA condition. [ABSTRACT FROM AUTHOR]

Potassium (K) is an essential macronutrient for plant growth, and its availability in the soil varies widely, requiring plants to respond and adapt to the changing K nutrient status. We show here that plant growth rate is closely correlated with K status in the medium, and this K-dependent growth is mediated by the highly conserved nutrient sensor, target of rapamycin (TOR). Further study connected the TOR complex (TORC) pathway with a low-K response signaling network consisting of calcineurin B-like proteins (CBL) and CBL-interacting kinases (CIPK). Under high K conditions, TORC is rapidly activated and shut down the CBL-CIPK low-K response pathway through regulatory-associated protein of TOR (RAPTOR)-CIPK interaction. In contrast, low-K status activates CBL-CIPK modules that in turn inhibit TORC by phosphorylating RAPTOR, leading to dissociation and thus inactivation of the TORC. The reciprocal regulation of the TORC and CBL-CIPK modules orchestrates plant response and adaptation to K nutrient status in the environment. [ABSTRACT FROM AUTHOR]

Phosphorus is essential to plant growth and agricultural crop yields, yet the challenges associated with phosphorus fertilization in agriculture, such as aquatic runoff pollution and poor phosphorus bioavailability, are increasingly difficult to manage. Comprehensively understanding the dynamics of phosphorus uptake and signaling mechanisms will inform the development of strategies to address these issues. This review describes regulatory mechanisms used by specific tissues in the root apical meristem to sense and take up phosphate from the rhizosphere. The major regulatory mechanisms and related hormone crosstalk underpinning phosphate starvation responses, cellular phosphate homeostasis, and plant adaptations to phosphate starvation are also discussed, along with an overview of the major mechanism of plant systemic phosphate starvation responses. Finally, this review discusses recent promising genetic engineering strategies for improving crop phosphorus use and computational approaches that may help further design strategies for improved plant phosphate acquisition. The mechanisms and approaches presented include a wide variety of species including not only Arabidopsis but also crop species such as Oryza sativa (rice), Glycine max (soybean), and Triticum aestivum (wheat) to address both general and species-specific mechanisms and strategies. The aspects of phosphorus deficiency responses and recently employed strategies of improving phosphate acquisition that are detailed in this review may provide insights into the mechanisms or phenotypes that may be targeted in efforts to improve crop phosphorus content and plant growth in low phosphorus soils. [ABSTRACT FROM AUTHOR]

Lysosomes sense glucose availability through modulations in mTORC1 signaling via Rag GTPases, PFKFB3, HK2, dihydroxyacetone phosphate, and GAPDH. Lysosomes sense glucose availability through AMPK signaling via the enzyme's aldolase and GAPDH. The mechanisms of glycogen transport to lysosomes are not clear. In the liver, there is evidence of an STBD1-dependent mechanism of glycogen transport to lysosomes, while in skeletal muscle there is some evidence of an STBD1-independent mechanism through macroautophagy. Lysosomes isolated from mouse liver contain GLUT1, 2, and 8 in addition to the SPNS1 glucose transporter, while lysosomes isolated from kidney cells contain GLUT8 and SPNS1, in addition to GLUT1 and 3 when mTORC1 is inhibited. Dysregulated lysosomal glucose sensing and glycophagy occurs in metabolic diseases such as cancer, insulin resistance, and hyperglycemia. Lysosomes are cellular organelles that function to catabolize both extra- and intracellular cargo, act as a platform for nutrient sensing, and represent a core signaling node integrating bioenergetic cues to changes in cellular metabolism. Although lysosomal amino acid and lipid sensing in metabolism has been well characterized, lysosomal glucose sensing and the role of lysosomes in glucose metabolism is unrefined. This review will highlight the role of the lysosome in glucose metabolism with a focus on lysosomal glucose and glycogen sensing, glycophagy, and lysosomal glucose transport and how these processes impact autophagy and energy metabolism. Additionally, the role of lysosomal glucose metabolism in genetic and metabolic diseases will be briefly discussed. [ABSTRACT FROM AUTHOR]

Accurate nutrient sensing is important for rapid fungal growth and exploitation of available resources. Sulfur is an important nutrient source found in a number of biological macromolecules, including proteins and lipids. The model filamentous fungus Neurospora crassa is capable of utilizing sulfur found in a variety of sources from amino acids to sulfate. During sulfur starvation, the transcription factor CYS-3 is responsible for upregulation of genes involved in sulfur uptake and assimilation. Using a combination of RNA sequencing and DNA affinity purification sequencing, we performed a global survey of the N. crassa sulfur starvation response and the role of CYS-3 in regulating sulfur-responsive genes. The CYS-3 transcription factor bound the promoters and regulated genes involved in sulfur metabolism. Additionally, CYS-3 directly activated the expression of a number of uncharacterized transporter genes, suggesting that regulation of sulfur import is an important aspect of regulation by CYS-3. CYS-3 also directly regulated the expression of genes involved in mitochondrial electron transfer. During sulfur starvation, genes involved in nitrogen metabolism, such as amino acid and nucleic acid metabolic pathways, along with genes encoding proteases and nucleases that are necessary for scavenging nitrogen, were activated. Sulfur starvation also caused changes in the expression of genes involved in carbohydrate metabolism, such as those encoding glycosyl hydrolases. Thus, our data suggest a connection between sulfur metabolism and other aspects of cellular metabolism. IMPORTANCE Identification of nutrients present in the environment is a challenge common to all organisms. Sulfur is an important nutrient source found in proteins, lipids, and electron carriers that are required for the survival of filamentous fungi such as Neurospora crassa. Here, we transcriptionally profiled the response of N. crassa to characterize the global response to sulfur starvation. We also used DNA affinity purification sequencing to identify the direct downstream targets of the transcription factor responsible for regulating genes involved in sulfur uptake and assimilation. Along with genes involved in sulfur metabolism, this transcription factor regulated a number of uncharacterized transporter genes and genes involved in mitochondrial electron transfer. Our data also suggest a connection between sulfur, nitrogen, and carbon metabolism, indicating that the regulation of a number of metabolic pathways is intertwined.

Abstract Background Adaptation to complex, rapidly changing environments is crucial for evolutionary success of fungi. The heterotrimeric G-protein pathway belongs to the most important signaling cascades applied for this task. In Trichoderma reesei, enzyme production, growth and secondary metabolism are among the physiological traits influenced by the G-protein pathway in a light dependent manner. Results Here, we investigated the function of the SNX/H-type regulator of G-protein signaling (RGS) protein RGS4 of T. reesei. We show that RGS4 is involved in regulation of cellulase production, growth, asexual development and oxidative stress response in darkness as well as in osmotic stress response in the presence of sodium chloride, particularly in light. Transcriptome analysis revealed regulation of several ribosomal genes, six genes mutated in RutC30 as well as several genes encoding transcription factors and transporters. Importantly, RGS4 positively regulates the siderophore cluster responsible for fusarinine C biosynthesis in light. The respective deletion mutant shows altered growth on nutrient sources related to siderophore production such as ornithine or proline in a BIOLOG phenotype microarray assay. Additionally, growth on storage carbohydrates as well as several intermediates of the D-galactose and D-arabinose catabolic pathway is decreased, predominantly in light. Conclusions We conclude that RGS4 mainly operates in light and targets plant cell wall degradation, siderophore production and storage compound metabolism in T. reesei.

Organisms must accurately sense and respond to nutrients to survive. In filamentous fungi, accurate nutrient sensing is important in the establishment of fungal colonies and in continued, rapid growth for the exploitation of environmental resources. To ensure efficient nutrient utilization, fungi have evolved a combination of activating and repressing genetic networks to tightly regulate metabolic pathways and distinguish between preferred nutrients, which require minimal energy and resources to utilize, and nonpreferred nutrients, which have more energy-intensive catabolic requirements. Genes necessary for the utilization of nonpreferred carbon sources are activated by transcription factors that respond to the presence of the specific nutrient and repressed by transcription factors that respond to the presence of preferred carbohydrates. Utilization of nonpreferred nitrogen sources generally requires two transcription factors. Pathway-specific transcription factors respond to the presence of a specific nonpreferred nitrogen source, while another transcription factor activates genes in the absence of preferred nitrogen sources. In this review, we discuss the roles of transcription factors and upstream regulatory genes that respond to preferred and nonpreferred carbon and nitrogen sources and their roles in regulating carbon and nitrogen catabolism. Key points: • Interplay of activating and repressing transcriptional networks regulates catabolism. • Nutrient-specific activating transcriptional pathways provide metabolic specificity. • Repressing regulatory systems differentiate nutrients in mixed nutrient environments. [ABSTRACT FROM AUTHOR]

To ensure survival and promote growth, sessile plants have developed intricate internal signaling networks tailored in diverse cells and organs with both shared and specialized functions that respond to various internal and external cues. A fascinating question arises: how can a plant cell or organ diagnose the spatial and temporal information it is experiencing to know "where I am," and then is able to make the accurate specific responses to decide "where to go" and "how to go," despite the absence of neuronal systems found in mammals. Drawing inspiration from recent comprehensive investigations into diverse nutrient signaling pathways in plants, this review focuses on the interactive nutrient signaling networks mediated by various nutrient sensors and transducers. We assess and illustrate examples of how cells and organs exhibit specific responses to changing spatial and temporal information within these interactive plant nutrient networks. In addition, we elucidate the underlying mechanisms by which plants employ posttranslational modification codes to integrate different upstream nutrient signals, thereby conferring response specificities to the signaling hub proteins. Furthermore, we discuss recent breakthrough studies that demonstrate the potential of modulating nutrient sensing and signaling as promising strategies to enhance crop yield, even with reduced fertilizer application. Plants have intricate signaling networks that respond to internal and external cues. This review focuses on nutrient signaling pathways mediated by sensors and transducers, and analyze recent studies about how cells and organs respond to spatial and temporal information within these networks. Furthermore, the authors discuss the integration of nutrient signals through posttranslational modifications and the potential of modulating nutrient sensing to enhance crop yield. [ABSTRACT FROM AUTHOR]

Sensing available nutrients and efficiently utilizing them is a challenge common to all organisms. The model filamentous fungus Neurospora crassa is capable of utilizing a variety of inorganic and organic nitrogen sources. Nitrogen utilization in N. crassa is regulated by a network of pathway-specific transcription factors that activate genes necessary to utilize specific nitrogen sources in combination with nitrogen catabolite repression regulatory proteins. We identified an uncharacterized pathway-specific transcription factor, amn-1, that is required for utilization of the nonpreferred nitrogen sources proline, branched-chain amino acids, and aromatic amino acids. AMN-1 also plays a role in regulating genes involved in responding to the simple sugar mannose, suggesting an integration of nitrogen and carbon metabolism. The utilization of nonpreferred nitrogen sources, which require metabolic processing before being used as a nitrogen source, is also regulated by the nitrogen catabolite regulator NIT-2. Using RNA sequencing combined with DNA affinity purification sequencing, we performed a survey of the role of NIT-2 and the pathway-specific transcription factors NIT-4 and AMN-1 in directly regulating genes involved in nitrogen utilization. Although previous studies suggested promoter binding by both a pathway-specific transcription factor and NIT-2 may be necessary for activation of nitrogen-responsive genes, our data show that pathway-specific transcription factors regulate genes involved in the catabolism of specific nitrogen sources, while NIT-2 regulates genes involved in utilization of all nonpreferred nitrogen sources, such as nitrogen transporters. Together, these transcription factors form a nutrient sensing network that allows N. crassa cells to regulate nitrogen utilization.

Feeding is vital for animal growth and the maintenance of health. However, the underlying mechanisms that mediate dietary performance have long been a so-called black box. It is only during recent years that studies have demonstrated that nutrients act as signals that can be sensed by cells and organisms and that play vital roles in gene expression and metabolism. Multiple signaling pathways have been identified as being responsible for the sensing of discrete nutrients. While successes have been achieved in the exploitation of nutrient-sensing signals in drug discovery and disease control, applications based on the sensing and metabolic control of major nutrients (proteins, lipids, carbohydrates, etc.) in land-farmed animals and aquaculture remain in their infancy. We thus provide a tentative perspective on future research topics and applications of nutrient sensing in animal nutrition.

Background/purpose: Metabolic syndrome (MetS) and overactive bladder might share common pathophysiologies. Environmental fructose exposure during pre- and postnatal periods of rats may program MetS-associated bladder overactivity. We explored the dysregulated insulin signalling at bladder mucosa, as a common mechanism, in facilitating bladder overactivity in rats with MetS induced by maternal and post-weaning fructose diet. Methods: Male offspring of Sprague–Dawley rats were subject into 4 groups by maternal and post-weaning diets (i.e., Control/Control, Fructose/Control, Control/Fructose and Fructose/Fructose by diets). Micturition behavior was evaluated. Acidic ATP solution was used to elicit cystometric reflex along with insulin counteraction. Concentration–response curves to insulin were plotted. The canonical signalling pathway of insulin was evaluated in the bladder mucosal using Western blotting. Levels of detrusor cGMP and urinary NO2 plus NO3 were measured. Results: Male offspring with any fructose exposure presents traits of MetS and bladder overactivity. We observed all fructose exposure groups have the poor urodynamic response to insulin during ATP solution stimulation and poor insulin-activated detrusor relaxation in organ bath study. Compared to controls, the Control/Fructose and Fructose/Fructose groups showed the increased phosphorylation levels of IRS1 (Ser307) and IRS2 (Ser731); thus, suppressed the downstream effectors and urinary NOx/detrusor cGMP levels. The Fructose/Control group showed the compensatory increase of phospho-AKT (Ser473) and phospho-eNOS/eNOS levels, but decreased in eNOS, phospho-eNOS, urinary NOx, and detrusor cGMP levels. Conclusion: Our results show dysregulated insulin signalling at bladder mucosa should be a common mechanism of MetS-associated bladder overactivity programmed by pre-and postnatal fructose diet.

Differentiation and fate decisions are critical for the epithelial cells lining the proximal tubule (PT) of the kidney, but the signals involved remain unknown. Defective cystine mobilization from lysosomes through CTNS (cystinosin, lysosomal cystine transporter), which is mutated in cystinosis, triggers the dedifferentiation and dysfunction of the PT cells, causing kidney disease and severe metabolic complications. Using preclinical models and physiologically relevant cellular systems, along with functional assays and a generative artificial intelligence (AI)-powered engine, we found that cystine storage imparted by CTNS deficiency stimulates Ragulator-RRAG GTPase-dependent recruitment of MTORC1 and its constitutive activation. In turn, this diverts the catabolic trajectories and differentiating states of PT cells toward growth and proliferation, disrupting homeostasis and their specialized functions. Therapeutic MTORC1 inhibition by using low doses of rapamycin corrects lysosome function and differentiation downstream of cystine storage and ameliorates PT dysfunction in preclinical models of cystinosis. These discoveries suggest that cystine may act as a lysosomal fasting signal that tailors MTORC1 signaling to direct fate decisions in the kidney PT epithelium, highlighting novel therapeutic paradigms for cystinosis and other lysosome-related disorders. [ABSTRACT FROM AUTHOR]

mTORC1 senses nutrients and growth factors and phosphorylates downstream targets, including the transcription factor TFEB, to coordinate metabolic supply and demand. These functions position mTORC1 as a central controller of cellular homeostasis, but the behavior of this system in individual cells has not been well characterized. Here, we provide measurements necessary to refine quantitative models for mTORC1 as a metabolic controller. We developed a series of fluorescent protein-TFEB fusions and a multiplexed immunofluorescence approach to investigate how combinations of stimuli jointly regulate mTORC1 signaling at the single-cell level. Live imaging of individual MCF10A cells confirmed that mTORC1-TFEB signaling responds continuously to individual, sequential, or simultaneous treatment with amino acids and the growth factor insulin. Under physiologically relevant concentrations of amino acids, we observe correlated fluctuations in TFEB, AMPK, and AKT signaling that indicate continuous activity adjustments to nutrient availability. Using partial least squares regression modeling, we show that these continuous gradations are connected to protein synthesis rate via a distributed network of mTORC1 effectors, providing quantitative support for the qualitative model of mTORC1 as a homeostatic controller and clarifying its functional behavior within individual cells.

Background: Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, the low-grade chronic inflammation during aging, without overt infection, is defined as “inflammaging,” which is associated with increased morbidity and mortality in the aging population. Emerging evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty. How the crosstalk between chronic inflammation and other hallmarks of aging underlies biological mechanisms of aging and age-related disease is thus of particular interest to the current geroscience research. Scope of review: This review integrates the cellular and molecular mechanisms of age-associated chronic inflammation with the other eleven hallmarks of aging. Extra discussion is dedicated to the hallmark of “altered nutrient sensing,” given the scope of Molecular Metabolism. The deregulation of hallmark processes during aging disrupts the delicate balance between pro-inflammatory and anti-inflammatory signaling, leading to a persistent inflammatory state. The resultant chronic inflammation, in turn, further aggravates the dysfunction of each hallmark, thereby driving the progression of aging and age-related diseases. Main conclusions: The crosstalk between chronic inflammation and other hallmarks of aging results in a vicious cycle that exacerbates the decline in cellular functions and promotes aging. Understanding this complex interplay will provide new insights into the mechanisms of aging and the development of potential anti-aging interventions. Given their interconnectedness and ability to accentuate the primary elements of aging, drivers of chronic inflammation may be an ideal target with high translational potential to address the pathological conditions associated with aging.

Background: Adaptation to complex, rapidly changing environments is crucial for evolutionary success of fungi. The heterotrimeric G-protein pathway belongs to the most important signaling cascades applied for this task. In Trichoderma reesei, enzyme production, growth and secondary metabolism are among the physiological traits influenced by the G-protein pathway in a light dependent manner. Results: Here, we investigated the function of the SNX/H-type regulator of G-protein signaling (RGS) protein RGS4 of T. reesei. We show that RGS4 is involved in regulation of cellulase production, growth, asexual development and oxidative stress response in darkness as well as in osmotic stress response in the presence of sodium chloride, particularly in light. Transcriptome analysis revealed regulation of several ribosomal genes, six genes mutated in RutC30 as well as several genes encoding transcription factors and transporters. Importantly, RGS4 positively regulates the siderophore cluster responsible for fusarinine C biosynthesis in light. The respective deletion mutant shows altered growth on nutrient sources related to siderophore production such as ornithine or proline in a BIOLOG phenotype microarray assay. Additionally, growth on storage carbohydrates as well as several intermediates of the D-galactose and D-arabinose catabolic pathway is decreased, predominantly in light. Conclusions: We conclude that RGS4 mainly operates in light and targets plant cell wall degradation, siderophore production and storage compound metabolism in T. reesei. [ABSTRACT FROM AUTHOR]

Amiodarone (AMD) is an antiarrhythmic drug prescribed to treat ventricular tachycardia and fibrillation. However, it causes an unpredictable toxicity (idiosyncratic), which may depend on co‐exposure to pollutants. AMD toxicity involves calcium homeostasis alteration and oxidative stress, which are also affected by cigarette smoke (CS). We investigated the interaction of CS‐condensate (CSC), phenanthrene, and benzo(a)pyrene with AMD toxicity on Saccharomyces cerevisiae. AMD toxicity was reduced by CSC or phenanthrene. Benzo(a)pyrene mildly decreased AMD toxicity on the wild‐type strain, but not on the catalase‐CTT1 mutant. This latter and other mutants in glucose receptor‐GPR1 or calcium transporter‐PMR1 showed lower antagonistic effect to AMD by CSC or phenanthrene relative to the wild type, suggesting roles of oxidative stress, calcium homeostasis, and hexose‐sensing in this interaction. Amiodarone (AMD) is an antiarrhythmic drug prescribed to treat ventricular tachycardia and fibrillation. However, it causes an unpredictable toxicity (idiosyncratic), which may depend on co‐exposure to pollutants. AMD toxicity involves calcium homeostasis alteration and oxidative stress, which are also affected by cigarette smoke (CS). We investigated the interaction of CS‐condensate (CSC), phenanthrene, and benzo(a) pyrene with AMD toxicity on Saccharomyces cerevisiae. AMD toxicity was reduced by CSC or phenanthrene. Benzo(a)pyrene mildly decreased AMD toxicity on the wild‐type strain, but not on the catalase‐CTT1 mutant. This latter and other mutants in glucose receptor‐GPR1 or calcium transporter‐PMR1 showed lower antagonistic effect to AMD by CSC or phenanthrene relative to the wild type, suggesting roles of oxidative stress, calcium homeostasis, and hexose‐sensing in this interaction. [ABSTRACT FROM AUTHOR]

The lysosome is an essential catabolic organelle that consumes cellular biomass to regenerate basic building blocks that can fuel anabolic reactions. This simple view has evolved more recently to integrate novel functions of the lysosome as a key signaling center, which can steer the metabolic trajectory of cells in response to changes in nutrients, growth factors, and stress. Master protein kinases and transcription factors mediate the growth-promoting and catabolic activities of the lysosome and undergo a complex interplay that enables cellular adaptation to ever-changing metabolic conditions. Understanding how this coordination occurs will shed light on the fundamental logic of how the lysosome functions to control growth in the context of development, tissue homeostasis, and cancer.

Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level.

The detection of nutrients in the gut influences ongoing and future feeding behavior as well as the development of food preferences. In addition to nutrient sensing in the intestine, the hepatic portal vein plays a considerable role in detecting ingested nutrients and conveying this information to brain nuclei involved in metabolism, learning, and reward. Here, we review mechanisms underlying hepatic portal vein sensing of nutrients, particularly glucose, and how this is relayed to the brain to influence feeding behavior and reward. We additionally highlight several gaps where future research can provide new insights into the effects of portal nutrients on neural activity in the brain and feeding behavior.

Extracellular signal‐regulated kinase 7 (ERK7), also known as ERK8 and MAPK15, is an atypical member of the MAP kinase family. Compared with other MAP kinases, the biological roles of ERK7 remain poorly understood. Recent work, however, has revealed several novel functions for ERK7. These include a highly conserved essential role in ciliogenesis, the ability to control cell growth, metabolism and autophagy, as well as the maintenance of genomic integrity. ERK7 functions through phosphorylation‐dependent and ‐independent mechanisms and it is activated by cellular stressors, including DNA‐damaging agents, and nutrient deprivation. Here, we summarize recent developments in understanding ERK7 function, emphasizing its conserved roles in cellular and physiological regulation. [ABSTRACT FROM AUTHOR]

Phosphorus (P) and nitrogen (N) are the major nutrients that constrain plant and algal growth in nature. Recent advances in understanding nutrient signalling mechanisms of these organisms have revealed molecular attributes to optimise N and P acquisition. This has illuminated the importance of interplay between N and P regulatory networks, highlighting a need to study synergistic interactions rather than single-nutrient effects. Emerging insights of nutrient signalling in polyphyletic model plants and algae hint that, although core P-starvation signalling components are conserved, distinct mechanisms for P (and N) sensing have arisen. Here, the N and P signalling mechanisms of diverse photosynthetic eukaryotes are examined, drawing parallels and differences between taxa. Future directions to understand their molecular basis, evolution, and ecology are proposed. The expansion of sequencing resources and the development of advanced plant and algal model systems provide a new framework to examine the distribution and evolution of N and P signalling mechanisms in photosynthetic eukaryotes. This has revealed that, although core P-starvation signalling components are conserved, distinct mechanisms for P (and N) sensing may have arisen. Ca2+ signalling is emerging as an important player in N and P sensing in photosynthetic eukaryotes, albeit that distinct roles have evolved in different lineages. Sophisticated mechanisms to integrate N and P signalling networks and maximise nutrient acquisition are employed by diverse photosynthetic eukaryotes. Integration of plant and algal research will expedite advances in our understanding of N and P signalling, and inform strategies to engineer improved N and P use efficiency in crops. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) and overactive bladder might share common pathophysiologies. Environmental fructose exposure during pre- and postnatal periods of rats may program MetS-associated bladder overactivity. We explored the dysregulated insulin signalling at bladder mucosa, as a common mechanism, in facilitating bladder overactivity in rats with MetS induced by maternal and post-weaning fructose diet. Male offspring of Sprague–Dawley rats were subject into 4 groups by maternal and post-weaning diets (i.e., Control/Control, Fructose/Control, Control/Fructose and Fructose/Fructose by diets). Micturition behavior was evaluated. Acidic ATP solution was used to elicit cystometric reflex along with insulin counteraction. Concentration–response curves to insulin were plotted. The canonical signalling pathway of insulin was evaluated in the bladder mucosal using Western blotting. Levels of detrusor cGMP and urinary NO 2 plus NO 3 were measured. Male offspring with any fructose exposure presents traits of MetS and bladder overactivity. We observed all fructose exposure groups have the poor urodynamic response to insulin during ATP solution stimulation and poor insulin-activated detrusor relaxation in organ bath study. Compared to controls, the Control/Fructose and Fructose/Fructose groups showed the increased phosphorylation levels of IRS1 (Ser307) and IRS2 (Ser731); thus, suppressed the downstream effectors and urinary NOx/detrusor cGMP levels. The Fructose/Control group showed the compensatory increase of phospho-AKT (Ser473) and phospho-eNOS/eNOS levels, but decreased in eNOS, phospho-eNOS, urinary NOx, and detrusor cGMP levels. Our results show dysregulated insulin signalling at bladder mucosa should be a common mechanism of MetS-associated bladder overactivity programmed by pre-and postnatal fructose diet. [ABSTRACT FROM AUTHOR]

In this study, an electrochemical sensor was developed by immobilizing colon cancer and the adjacent tissues (peripheral healthy tissues on both sides of the tumor) and was used to investigate the receptor sensing kinetics of glucose, sodium glutamate, disodium inosinate, and sodium lactate. The results showed that the electrical signal triggered by the ligand–receptor interaction presented hyperbolic kinetic characteristics similar to the interaction of an enzyme with its substrate. The results indicated that the activation constant values of the colon cancer tissue and adjacent tissues differed by two orders of magnitude for glucose and sodium glutamate and around one order of magnitude for disodium inosinate. The cancer tissues did not sense sodium lactate, whereas the adjacent tissues could sense sodium lactate. Compared with normal cells, cancer cells have significantly improved nutritional sensing ability, and the improvement of cancer cells' sensing ability mainly depends on the cascade amplification of intracellular signals. However, unlike tumor-adjacent tissues, colon cancer cells lose the ability to sense lactate. This provides key evidence for the Warburg effect of cancer cells. The methods and results in this study are expected to provide a new way for cancer research, treatment, the screening of anticancer drugs, and clinical diagnoses. [ABSTRACT FROM AUTHOR]

Objective: Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are unknown. The aim of this study was to characterize myelin plasticity in the ME of adult mice in health or in response to chronic nutritional challenge and determine its relevance to the regulation of energy balance. Methods: We assessed new oligodendrocyte (OL) and myelin generation and stability in the ME of healthy adult male mice using bromodeoxyuridine labelling and genetic fate mapping tools. We evaluated the contribution of microglia to ME myelin plasticity in PLX5622-treated C57BL/6J mice and in Pdgfra-Cre/ERT2;R26R-eYFP;Myrffl/fl mice, where adult oligodendrogenesis is blunted. Next, we investigated how high-fat feeding or caloric restriction impact ME OL lineage progression and myelination. Finally, we characterized the functional relevance of adult oligodendrogenesis on energy balance regulation. Results: We show that myelinating OLs are continuously and rapidly generated in the adult ME. Paradoxically, OL number and myelin amounts remain remarkably stable in the adult ME. In fact, the high rate of new OL and myelin generation in the ME is offset by continuous turnover of both. We show that microglia are required for continuous OL and myelin production, and that ME myelin plasticity regulates the recruitment of local immune cells. Finally, we provide evidence that ME myelination is regulated by the body’s energetic status and demonstrate that ME OL and myelin plasticity are required for the regulation of energy balance and hypothalamic leptin sensitivity. Conclusions: This study identifies a new mechanism modulating leptin sensitivity and the central control of energy balance and uncovers a previously unappreciated form of structural plasticity in the ME.

Tremendous progress has been made in the field of ferroptosis since this regulated cell death process was first named in 2012. Ferroptosis is initiated upon redox imbalance and driven by excessive phospholipid peroxidation. Levels of multiple intracellular nutrients (iron, selenium, vitamin E and coenzyme Q10) are intimately related to the cellular antioxidant system and participate in the regulation of ferroptosis. Dietary intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) regulates ferroptosis by directly modifying the fatty acid composition in cell membranes. In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Understanding the molecular interaction between nutrient signals and ferroptosis sensors might help in the identification of the roles of ferroptosis in normal physiology and in the development of novel pharmacological targets for the treatment of ferroptosis-related diseases. [ABSTRACT FROM AUTHOR]

To survive and sustain growth, sessile plants have developed sophisticated internal signalling networks that respond to various external and internal cues. Despite the central roles of nutrient and hormone signaling in plant growth and development, how hormone-driven processes coordinate with metabolic status remains largely enigmatic. Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, hormones, and stress signals to promote growth in all eukaryotes. Inspired by recent comprehensive systems, chemical, genetic, and genomic studies on TOR in plants, this review discusses a potential role of TOR as a 'global positioning system' that directs plant growth and developmental programs both temporally and spatially by integrating dynamic information in the complex nutrient and hormonal signaling networks. We further evaluate and depict the possible functional and mechanistic models for how a single protein kinase, TOR, is able to recognize, integrate, and even distinguish a plethora of positive and negative input signals to execute appropriate and distinct downstream biological processes via multiple partners and effectors. [ABSTRACT FROM AUTHOR]

Target of rapamycin complex 1 (TORC1) is a highly conserved serine–threonine protein kinase crucial for coordinating growth according to nutrient availability in eukaryotes. It works as a central integrator of multiple nutrient inputs such as sugar, nitrogen, and phosphate and promotes growth and biomass accumulation in response to nutrient sufficiency. Studies, especially in the past decade, have identified the central role of TORC1 in regulating growth through interaction with hormones, photoreceptors, and stress signaling machinery in plants. In this review, we comprehensively analyse the interactome and phosphoproteome of the Arabidopsis TORC1 signaling network. Our analysis highlights the role of TORC1 as a central hub kinase communicating with the transcriptional and translational apparatus, ribosomes, chaperones, protein kinases, metabolic enzymes, and autophagy and stress response machinery to orchestrate growth in response to nutrient signals. This analysis also suggests that along with the conserved downstream components shared with other eukaryotic lineages, plant TORC1 signaling underwent several evolutionary innovations and co-opted many lineage-specific components during. Based on the protein–protein interaction and phosphoproteome data, we also discuss several uncharacterized and unexplored components of the TORC1 signaling network, highlighting potential links for future studies. [ABSTRACT FROM AUTHOR]

The potential role of proteinase activated receptor 2 (PAR2) in the development of age-related obesity and insulin resistance is not well-understood. To address the hypothesis that deletion of PAR2 might ameliorate age-related obesity and impaired glucose homeostasis, we assessed body composition and insulin action in 18-month-old male PAR2 knockout (PAR2KO-AG), age-matched (AG) and young C57BL6 (YG, 6-month-old) mice. Body composition was measured by magnetic resonance spectroscopy (MRS) and insulin action was assessed by glucose tolerance (GT), insulin tolerance (IT) and AICAR tolerance (AT) testing. AG mice weighed significantly more than YG mice (p = 0.0001) demonstrating age-related obesity. However, PAR2KO-AG mice weighed significantly more than AG mice (p = 0.042), indicating that PAR2 may prevent a portion of age-related obesity. PAR2KO-AG and AG mice had greater fat mass and body fat percentage than YG mice. Similar to body weight, fat mass was greater in PAR2KO-AG mice compared to AG mice (p = 0.045); however, only a trend for greater body fat percentage in PAR2KO-AG compared to AG mice was observed (p = 0.09). No differences existed in lean body mass among the PAR2KO-AG, AG, and YG mice (p = 0.58). With regard to insulin action, the area under the curve (AUC) for GT was lower in PAR2KO-AG compared to AG mice (p = 0.0003) and YG mice (p = 0.001); however, no differences existed for the AUC for IT or AT. Our findings indicate that age-related obesity is not dependent on PAR2 expression. [ABSTRACT FROM AUTHOR]

The original description of dietary methionine restriction (MR) used semipurified diets to limit methionine intake to 20% of normal levels, and this reduction in dietary methionine increased longevity by ∼30% in rats. The MR diet also produces paradoxical increases in energy intake and expenditure and limits fat deposition while reducing tissue and circulating lipids and enhancing overall insulin sensitivity. In the years following the original 1993 report, a comprehensive effort has been made to understand the nutrient sensing and signaling systems linking reduced dietary methionine to the behavioral, physiological, biochemical, and transcriptional components of the response. Recent work has shown that transcriptional activation of hepatic fibroblast growth factor 21 (FGF21) is a key event linking the MR diet to many but not all components of its metabolic phenotype. These findings raise the interesting possibility of developing therapeutic, MR-based diets that produce the beneficial effects of FGF21 by nutritionally modulating its transcription and release. [ABSTRACT FROM AUTHOR]

Water and soil nutrients are the vital ingredients of crop production, and their efficient uptake is essentially dependent on root development, majorly regulated by auxin. For a water-loving crop like rice, how water availability regulates nutrient acquisition, additionally, how ambient nutrient level modulates water uptake, and the role of auxin therein is not well studied. While investigating the cross-talks among these components, we found water to be essential for auxin re-distribution in roots and shaping the root architecture. We also found that supplementing rice seedlings with moderate concentrations of mineral nutrients facilitated faster water uptake and greater nutrient enrichment in leaves compared to adequate nutrient supplementation. Additionally, moderate nutrient availability favoured greater stomatal density, stomatal conductance, photosynthesis, transpiration rate and water use efficiency when water was not limiting. Further, auxin supplementation enhanced root formation in rice, while affecting their water uptake ability, photosynthesis and transpiration causing differential mineral-specific uptake trends. The present study uncovers the existence of an intricate crosstalk among water, nutrients and auxin signalling the knowledge of which will enable optimizing the growth conditions for speed breeding of rice and harnessing the components of auxin signalling to improve water and nutrient use efficiency of rice., (© 2024 John Wiley & Sons Ltd.)

The human pathogen Pseudomonas aeruginosa , a leading cause of hospital-acquired infections, inhabits and forms sessile antibiotic-resistant communities called biofilms in a wide range of biotic and abiotic environments. In this study, we examined how two global sensory signaling pathways-the RhlR quorum-sensing system and the CbrA/CbrB nutritional adaptation system-intersect to control biofilm development. Previous work has shown that individually these two systems repress biofilm formation. Here, we used biofilm analyses, RNA-seq, and reporter assays to explore the combined effect of information flow through RhlR and CbrA on biofilm development. We find that the Δ rhlR Δ cbrA double mutant exhibits a biofilm morphology and an associated transcriptional response distinct from wildtype and the parent Δ rhlR and Δ cbrA mutants indicating codominance of each signaling pathway. The Δ rhlR Δ cbrA mutant gains suppressor mutations that allow biofilm expansion; these mutations map to the crc gene resulting in loss of function of the carbon catabolite repression protein Crc. Furthermore, the combined absence of RhlR and CbrA leads to a drastic reduction in the abundance of the Crc antagonist small RNA CrcZ. Thus, CrcZ acts as the molecular convergence point for quorum- and nutrient-sensing cues. We find that in the absence of antagonism by CrcZ, Crc promotes the expression of biofilm matrix components-Pel exopolysaccharide, and CupB and CupC fimbriae. Therefore, this study uncovers a regulatory link between nutritional adaption and quorum sensing with potential implications for anti-biofilm targeting strategies.IMPORTANCEBacteria often form multicellular communities encased in an extracytoplasmic matrix called biofilms. Biofilm development is controlled by various environmental stimuli that are decoded and converted into appropriate cellular responses. To understand how information from two distinct stimuli is integrated, we used biofilm formation in the human pathogen Pseudomonas aeruginosa as a model and studied the intersection of two global sensory signaling pathways-quorum sensing and nutritional adaptation. Global transcriptomics on biofilm cells and reporter assays suggest parallel regulation of biofilms by each pathway that converges on the abundance of a small RNA antagonist of the carbon catabolite repression protein, Crc. We find a new role of Crc as it modulates the expression of biofilm matrix components in response to the environment. These results expand our understanding of the genetic regulatory strategies that allow P. aeruginosa to successfully develop biofilm communities., Competing Interests: The authors declare no conflict of interest.