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Plant Signaling & Behavior Dec 2024One of the main signal transduction pathways that modulate plant growth and stress responses, including drought, is the action of phytohormones. Recent advances in omics...
One of the main signal transduction pathways that modulate plant growth and stress responses, including drought, is the action of phytohormones. Recent advances in omics approaches have facilitated the exploration of plant genomes. However, the molecular mechanisms underlying the response in the crown of barley, which plays an essential role in plant performance under stress conditions and regeneration after stress treatment, remain largely unclear. The objective of the present study was the elucidation of drought-induced molecular reactions in the crowns of different barley phytohormone mutants. We verified the hypothesis that defects of gibberellins, brassinosteroids, and strigolactones action affect the transcriptomic, proteomic, and hormonal response of barley crown to the transitory drought influencing plant development under stress. Moreover, we assumed that due to the strong connection between strigolactones and branching the mutant, with dysfunctional receptor of strigolactones, manifests the most abundant alternations in crowns and phenotype under drought. Finally, we expected to identify components underlying the core response to drought which are independent of the genetic background. Large-scale analyses were conducted using gibberellins-biosynthesis, brassinosteroids-signaling, and strigolactones-signaling mutants, as well as reference genotypes. Detailed phenotypic evaluation was also conducted. The obtained results clearly demonstrated that hormonal disorders caused by mutations in the , , and genes affected the multifaceted reaction of crowns to drought, although the expression of these genes was not induced by stress. The study further detected not only genes and proteins that were involved in the drought response and reacted specifically in mutants compared to the reaction of reference genotypes and , but also the candidates that may underlie the genotype-universal stress response. Furthermore, candidate genes involved in phytohormonal interactions during the drought response were identified. We also found that the interplay between hormones, especially gibberellins and auxins, as well as strigolactones and cytokinins may be associated with the regulation of branching in crowns exposed to drought. Overall, the present study provides novel insights into the molecular drought-induced responses that occur in barley crowns.
Topics: Hordeum; Plant Growth Regulators; Droughts; Mutation; Gibberellins; Gene Expression Regulation, Plant; Brassinosteroids; Plant Proteins; Stress, Physiological; Lactones
PubMed: 38923879
DOI: 10.1080/15592324.2024.2371693 -
ELife Jun 2024Cognitive decline is a significant health concern in our aging society. Here, we used the model organism to investigate the impact of the IIS/FOXO pathway on...
Cognitive decline is a significant health concern in our aging society. Here, we used the model organism to investigate the impact of the IIS/FOXO pathway on age-related cognitive decline. The Insulin/IGF-1 receptor mutant exhibits a significant extension of learning and memory span with age compared to wild-type worms, an effect that is dependent on the DAF-16 transcription factor. To identify possible mechanisms by which aging mutants maintain learning and memory with age while wild-type worms lose neuronal function, we carried out neuron-specific transcriptomic analysis in aged animals. We observed downregulation of neuronal genes and upregulation of transcriptional regulation genes in aging wild-type neurons. By contrast, IIS/FOXO pathway mutants exhibit distinct neuronal transcriptomic alterations in response to cognitive aging, including upregulation of stress response genes and downregulation of specific insulin signaling genes. We tested the roles of significantly transcriptionally-changed genes in regulating cognitive functions, identifying novel regulators of learning and memory. In addition to other mechanistic insights, a comparison of the aged vs young neuronal transcriptome revealed that a new set of potentially neuroprotective genes is upregulated; instead of simply mimicking a young state, may enhance neuronal resilience to accumulation of harm and take a more active approach to combat aging. These findings suggest a potential mechanism for regulating cognitive function with age and offer insights into novel therapeutic targets for age-related cognitive decline.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Forkhead Transcription Factors; Transcriptome; Neurons; Cognitive Aging; Aging; Receptor, Insulin; Signal Transduction; Gene Expression Regulation; Memory; Gene Expression Profiling
PubMed: 38922671
DOI: 10.7554/eLife.95621 -
Toxins May 2024produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of...
produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of plant pathogens, but may also play a role in interactions between competing fungi. We observed higher resistance to added fumonisin B (FB) in fumonisin-producing than in nonproducing , and likewise between isolates of and differing in production of sphinganine-analog toxins. It has been reported that in , ceramide synthase encoded in the fumonisin biosynthetic gene cluster is responsible for self-resistance. We reinvestigated the role of and by generating a double mutant strain in a background. Nearly unchanged resistance to added FB was observed compared to the parental strain. A recently developed fumonisin-sensitive baker's yeast strain allowed for the testing of candidate ceramide synthases by heterologous expression. The overexpression of the yeast gene, but not , increased fumonisin resistance. High-level resistance was conferred by , but not by . Likewise, strong resistance to FB was caused by overexpression of the presumed "housekeeping" ceramide synthases , , and , located outside the fumonisin cluster, indicating that possesses a redundant set of insensitive targets as a self-resistance mechanism.
Topics: Fumonisins; Fusarium; Oxidoreductases; Drug Resistance, Fungal; Fungal Proteins; Aspergillus; Alternaria
PubMed: 38922130
DOI: 10.3390/toxins16060235 -
ELife Jun 2024mutation is a driver mutation in the serrated pathway to colorectal cancers. BRAF drives tumorigenesis through constitutive downstream extracellular signal-regulated...
mutation is a driver mutation in the serrated pathway to colorectal cancers. BRAF drives tumorigenesis through constitutive downstream extracellular signal-regulated kinase (ERK) activation, but high-intensity ERK activation can also trigger tumor suppression. Whether and how oncogenic ERK signaling can be intrinsically adjusted to a 'just-right' level optimal for tumorigenesis remains undetermined. In this study, we found that FAK (Focal adhesion kinase) expression was reduced in -mutant adenomas/polyps in mice and patients. In ; mice, deletion maximized BRAF's oncogenic activity and increased cecal tumor incidence to 100%. Mechanistically, our results showed that Fak loss, without jeopardizing BRAF-induced ERK pathway transcriptional output, reduced EGFR (epidermal growth factor receptor)-dependent ERK phosphorylation. Reduction in ERK phosphorylation increased the level of Lgr4, promoting intestinal stemness and cecal tumor formation. Our findings show that a 'just-right' ERK signaling optimal for -induced cecal tumor formation can be achieved via Fak loss-mediated downregulation of ERK phosphorylation.
Topics: Animals; Proto-Oncogene Proteins B-raf; Phosphorylation; Mice; Humans; Cecal Neoplasms; Focal Adhesion Kinase 1; Extracellular Signal-Regulated MAP Kinases; MAP Kinase Signaling System; ErbB Receptors; Carcinogenesis; Receptors, G-Protein-Coupled; Male
PubMed: 38921956
DOI: 10.7554/eLife.94605 -
Pathogens (Basel, Switzerland) May 2024pv. () is a significant phytopathogen causing black rot disease in crucifers. Its virulence relies heavily on the type III secretion system (T3SS), facilitating...
pv. () is a significant phytopathogen causing black rot disease in crucifers. Its virulence relies heavily on the type III secretion system (T3SS), facilitating effector translocation into plant cells. The type III effectors (T3Es) disrupt cellular processes, promoting pathogen proliferation. However, only a few T3Es from have been thoroughly characterized. In this study, we further investigated two effectors using the T3Es-deficient mutant and the protoplast system. XopE2 triggers immune responses via an unidentified activator of the salicylic acid (SA) signaling pathway, whereas XopL suppresses the expression of genes associated with patterns-triggered immunity (PTI) and the SA signaling pathway. These two effectors exert opposing effects on immune responses. Additionally, we examined the relationship between the specific domains and functions of these two effector proteins. Our findings demonstrate that the N-myristoylation motif and N-terminal domain are essential for the subcellular localization and virulence of XopE2 and XopL, respectively. These novel insights enhance our understanding of the pathogenic mechanisms of T3Es and contribute to developing effective strategies for controlling bacterial disease.
PubMed: 38921746
DOI: 10.3390/pathogens13060448 -
Marine Drugs Jun 2024Sortase A (SrtA) is a cysteine transpeptidase that binds to the periplasmic membrane and plays a crucial role in attaching surface proteins, including staphylococcal...
Sortase A (SrtA) is a cysteine transpeptidase that binds to the periplasmic membrane and plays a crucial role in attaching surface proteins, including staphylococcal protein A (SpA), to the peptidoglycan cell wall. Six pentacyclic polyketides (-) were isolated from the marine sponge sp., and their structures were elucidated using spectroscopic techniques and by comparing them to previously reported data. Among them, halenaquinol () was found to be the most potent SrtA inhibitor, with an IC of 13.94 μM (4.66 μg/mL). Semi-quantitative reverse transcription PCR data suggest that halenaquinol does not inhibit the transcription of and , while Western blot analysis and immunofluorescence microscopy images suggest that it blocks the cell wall surface anchoring of SpA by inhibiting the activity of SrtA. The onset and magnitude of the inhibition of SpA anchoring on the cell wall surface in that has been treated with halenaquinol at a value 8× that of the IC of SrtA are comparable to those for an -deletion mutant. These findings contribute to the understanding of the mechanism by which marine-derived pentacyclic polyketides inhibit SrtA, highlighting their potential as anti-infective agents targeting virulence.
Topics: Aminoacyltransferases; Cysteine Endopeptidases; Staphylococcus aureus; Cell Wall; Bacterial Proteins; Animals; Porifera; Anti-Bacterial Agents; Polyketides
PubMed: 38921577
DOI: 10.3390/md22060266 -
Marine Drugs Jun 2024Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of...
Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of deepsea-derived SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains CCARM 5172 and CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 μg/mL.
Topics: Streptomyces; Lipopeptides; Microbial Sensitivity Tests; Anti-Bacterial Agents; Enterococcus faecalis; Peptides, Cyclic; Enterococcus faecium; Drug Resistance, Multiple, Bacterial; Bacterial Proteins
PubMed: 38921573
DOI: 10.3390/md22060262 -
Journal of Fungi (Basel, Switzerland) May 2024Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are central components of the machinery mediating cell membrane fusion and intracellular...
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are central components of the machinery mediating cell membrane fusion and intracellular vesicular trafficking in eukaryotic cells, and have been well-documented to play critical roles in growth, development, and pathogenesis in the filamentous fungal plant pathogens. However, little is known about the contributions of SNAREs to the physiology and biocontrol potential in entomopathogenic filamentous fungi. Here, a genome-wide analysis of SNARE genes was performed taking advantage of the available whole genome sequence of , a classical entomopathogenic fungus. Based on the compared genomic method, 22 genes encoding putative SNAREs were identified from the whole genome of , and were classified into four groups (7 Qa-, 4 Qb-, 6 Qc-, and 5 R-SNAREs) according to the conserved structural features of their encoding proteins. An R-SNARE encoding gene was further functionally characterized by gene disruption and complementation. The null mutant showed a fluffy appearance in mycelial growth and an obvious lag in conidial germination. The null mutant also exhibited significantly increased sensitivity to oxidative stress and cell wall perturbing agents and reduced the yield of conidia production by 43.1% compared with the wild-type strain. Moreover, disruption of caused a significant decrease in conidial virulence to larvae. Overall, our results provide an overview of vesicle trafficking in and revealed that BbSec22 was a multifunctional protein associated with mycelial growth, sporulation, conidial germination, stress tolerance, and insecticidal virulence.
PubMed: 38921379
DOI: 10.3390/jof10060393 -
Journal of Fungi (Basel, Switzerland) May 2024, a major postharvest pathogen, causes blue mold rot in citrus fruits through the deployment of various virulence factors. Recent studies highlight the role of the...
, a major postharvest pathogen, causes blue mold rot in citrus fruits through the deployment of various virulence factors. Recent studies highlight the role of the epigenetic reader, , in modulating the pathogenicity of phytopathogenic fungi. Our research revealed that the deletion of the gene in led to significant phenotypic alterations, including delayed mycelial growth, reduced spore production, and decreased utilization of sucrose. Additionally, the mutant strain exhibited increased sensitivity to pH fluctuations and elevated iron and calcium ion stress, culminating in reduced virulence on Gannan Novel oranges. Ultrastructural analyses disclosed notable disruptions in cell membrane integrity, disorganization within the cellular matrix, and signs of autophagy. Transcriptomic data further indicated a pronounced upregulation of hydrolytic enzymes, oxidoreductases, and transport proteins, suggesting a heightened energy demand. The observed phenomena were consistent with a carbon starvation response potentially triggering apoptotic pathways, including iron-dependent cell death. These findings collectively underscored the pivotal role of in maintaining the pathogenic traits of , proposing that targeting could offer a new avenue for controlling citrus fungal infections and subsequent fruit decay.
PubMed: 38921355
DOI: 10.3390/jof10060368 -
Cells Jun 2024Serine/threonine kinase AKT isoforms play a well-established role in cell metabolism and growth. Most pancreatic adenocarcinomas (PDACs) harbor activation mutations of...
Serine/threonine kinase AKT isoforms play a well-established role in cell metabolism and growth. Most pancreatic adenocarcinomas (PDACs) harbor activation mutations of KRAS, which activates the PI3K/AKT signaling pathway. However, AKT inhibitors are not effective in the treatment of pancreatic cancer. To better understand the role of AKT signaling in mutant-KRAS pancreatic tumors, this study utilized proteolysis-targeting chimeras (PROTACs) and CRISPR-Cas9-genome editing to investigate AKT proteins. The PROTAC down-regulation of AKT proteins markedly slowed the growth of three pancreatic tumor cell lines harboring mutant KRAS. In contrast, the inhibition of AKT kinase activity alone had very little effect on the growth of these cell lines. The concurrent genetic deletion of all AKT isoforms (AKT1, AKT2, and AKT3) in the KPC (; ; ) pancreatic cancer cell line also dramatically slowed its growth in vitro and when orthotopically implanted in syngeneic mice. Surprisingly, insulin-like growth factor-1 (IGF-1), but not epidermal growth factor (EGF), restored KPC cell growth in serum-deprived conditions, and the IGF-1 growth stimulation effect was AKT-dependent. The RNA-seq analysis of AKT1/2/3-deficient KPC cells suggested that reduced cholesterol synthesis may be responsible for the decreased response to IGF-1 stimulation. These results indicate that the presence of all three AKT isoforms supports pancreatic tumor cell growth, and the pharmacological degradation of AKT proteins may be more effective than AKT catalytic inhibitors for treating pancreatic cancer.
Topics: Proto-Oncogene Proteins c-akt; Pancreatic Neoplasms; Animals; Cell Line, Tumor; Mice; Humans; Down-Regulation; Proto-Oncogene Proteins p21(ras); Mutation; Cell Proliferation; Signal Transduction; Gene Expression Regulation, Neoplastic
PubMed: 38920688
DOI: 10.3390/cells13121061