Network Modeling Unravels Mechanisms of Crosstalk between Ethylene and Salicylate Signaling in Potato

Ramšak, Živa; Coll, Anna; Stare, Tjaša; Tzfadia, Oren; Baebler, Špela; Peer, Yves Van de; Gruden, Kristina

doi:10.1104/pp.18.00450

Cited by 41 publications

(37 citation statements)

References 64 publications

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“…High-throughput RT-qPCR was used to measure CCL5, CCR5 expression. RT-qPCR was performed with FAM-MGB probes with Fluidigm BioMark HD System RT-PCR (Fluidigm Corporation, San Francisco, CA, USA) using 48.48 Dynamic Arrays IFC [66], where 42 samples and 24 assays (probes) were mixed pairwise in nanoliter chambers to enable parallel analysis of 2304 reactions.…”

Section: Gene Expression Analysismentioning

confidence: 99%

CCR5-Mediated Signaling is Involved in Invasion of Glioblastoma Cells in Its Microenvironment

Novak

Krajnc

Hrastar

et al. 2020

IJMS

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The chemokine CCL5/RANTES is a versatile inflammatory mediator, which interacts with the receptor CCR5, promoting cancer cell interactions within the tumor microenvironment. Glioblastoma is a highly invasive tumor, in which CCL5 expression correlates with shorter patient survival. Using immunohistochemistry, we identified CCL5 and CCR5 in a series of glioblastoma samples and cells, including glioblastoma stem cells. CCL5 and CCR5 gene expression were significantly higher in a cohort of 38 glioblastoma samples, compared to low-grade glioma and non-cancerous tissues. The in vitro invasion of patients-derived primary glioblastoma cells and glioblastoma stem cells was dependent on CCL5-induced CCR5 signaling and is strongly inhibited by the small molecule CCR5 antagonist maraviroc. Invasion of these cells, which was enhanced when co-cultured with mesenchymal stem cells (MSCs), was inhibited by maraviroc, suggesting that MSCs release CCR5 ligands. In support of this model, we detected CCL5 and CCR5 in MSC monocultures and glioblastoma-associated MSC in tissue sections. We also found CCR5 expressing macrophages were in close proximity to glioblastoma cells. In conclusion, autocrine and paracrine cross-talk in glioblastoma and, in particular, glioblastoma stem cells with its stromal microenvironment, involves CCR5 and CCL5, contributing to glioblastoma invasion, suggesting the CCL5/CCR5 axis as a potential therapeutic target that can be targeted with repositioned drug maraviroc.

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Section: Gene Expression Analysismentioning

confidence: 99%

CCR5-Mediated Signaling is Involved in Invasion of Glioblastoma Cells in Its Microenvironment

Novak

Krajnc

Hrastar

et al. 2020

IJMS

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“…During the last decade, important technical improvements have slowly improved our knowledge on general mechanisms of defense response in PVY infection. This should improve even further with the implementation of mathematical modelling to predict responses of immune signaling [28] and linked primary metabolism. In addition, the production of PVY infectious clones [114][115][116] and advances in genetically encoded sensors in plants [117] will enable spatiotemporal monitoring of interactions between host and viral proteins during viral infection.…”

Section: Future Outlookmentioning

confidence: 99%

“…The studies in the model plants uncovered several aspects of molecular mechanisms in plant immunity [26]. Although some findings can be transferred to crop species using orthology [27,28], this is not always the case as, for example, in recently reported redundancy of Phytoalexin-deficient 4 (PAD4) in Solanaceae [29]. Therefore, it is important to perform the studies also in crop plants, such as potato.…”

Section: Introductionmentioning

confidence: 99%

Plant Molecular Responses to Potato Virus Y: A Continuum of Outcomes from Sensitivity and Tolerance to Resistance

Baebler

Coll

Gruden

2020

Viruses

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Potato virus Y (PVY) is the most economically important virus affecting potato production. PVY manipulates the plant cell machinery in order to successfully complete the infecting cycle. On the other side, the plant activates a sophisticated multilayer immune defense response to combat viral infection. The balance between these mechanisms, depending on the plant genotype and environment, results in a specific outcome that can be resistance, sensitivity, or tolerance. In this review, we summarize and compare the current knowledge on molecular events, leading to different phenotypic outcomes in response to PVY and try to link them with the known molecular mechanisms.

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“…To date, most of the studies of those processes were performed for the model plant Arabidopsis (Piquerez et al, 2014). Although some findings can be transferred to crop species using orthology (Lee et al, 2015;Ramšak et al, 2018) this is not always the case as, for example, in recently reported redundancy of PAD4 in Solanaceae (Gantner et al, 2019). Therefore it is important to perform the studies also in crop plants, such as potato.…”

Section: Discussionmentioning

confidence: 99%

Spatial accumulation of salicylic acid is regulated by RBOHD in potato immunity against viruses

Lukan¹,

Pompe-Novak²,

Baebler³

et al. 2020

Preprint

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Corresponding author: Tjaša Lukan (tjasa.lukan@nib.si). SIGNIFICANCETo get towards sustainable resistance in the field, it is important to understand mechanisms of immune signaling. We here show novel aspects of spatial regulation in effector-triggered immunity (ETI) against potato virus Y. A detailed spatiotemporal analysis in and surrounding the foci of viral infection, on ultrastructural, biochemical and gene expression levels revealed that redox state maintenance is tightly spatiotemporally regulated. We also show the interconnection of salicylic acid and RBOHD through a feedback loop, regulated through UDP-glucosyltransferase, revealing the mechanism of this spatial regulation. The proper function of this loop is essential for successful ETI leading to viral arrest. ABSTRACTWhile activation of resistance (R) proteins has been intensively studied, the mechanisms acting downstream of R protein activation remain elusive. We studied effector-triggered immunity (ETI) conditioned by the potato Ny-1 gene against potato virus Y. Transcriptomic, ultrastructural and biochemical analyses of four consecutive tissue sections in and surrounding the foci of viral infection at three different lesion developmental stages revealed processes that are spatiotemporally regulated.The transcriptional response in the cell death zone and surrounding tissue is dependent on SA. For 2 some of the genes, spatiotemporal regulation is completely lost while for others, the regulation is different in SA-deficient line indicating multiple connections between hormonal signaling modules. The induction of RBOHD NADPH oxidase expression, together with expression of Thioredoxin H gene, occurs specifically in the border region of the lesion during ETI. In plants with silenced RBOHD, ETI is perturbed and virus spread is not arrested at the site of infection. Expression of RBOHD is under the control of SA. On the other hand, RBOHD activity is required for spatial regulation of SA accumulation.We identified an UDP-glucosyltransferase, encoding an enzyme involved in feedback activation of SA biosynthesis, that is derepressed at the border of the lesion in RBOHD silenced plants. Altogether, we revealed a novel aspect of viral ETI, the RBOHD-SA feedback loop required for its spatial regulation.

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Network Modeling Unravels Mechanisms of Crosstalk between Ethylene and Salicylate Signaling in Potato

Cited by 41 publications

References 64 publications

CCR5-Mediated Signaling is Involved in Invasion of Glioblastoma Cells in Its Microenvironment

CCR5-Mediated Signaling is Involved in Invasion of Glioblastoma Cells in Its Microenvironment

Plant Molecular Responses to Potato Virus Y: A Continuum of Outcomes from Sensitivity and Tolerance to Resistance

Spatial accumulation of salicylic acid is regulated by RBOHD in potato immunity against viruses

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