Growing of the TOR world

Henriques, Rossana; Calderan-Rodrigues, Maria Juliana; Crespo, José L.; Baena-González, Elena; Caldana, Camila

doi:10.1093/jxb/erac401

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…Nevertheless, AZD-8055 and WYE-132 are both potent and selective ATP-competitive TOR inhibitors that can be used now in combination with the tor-15-resistant mutant to evaluate the specific TOR kinase-dependent effects observed in vivo in plants. This combination could also help re-evaluate the accuracy of some previously proposed plant TOR targets (Henriques et al, 2022). Knowing that the TOR sequence is well conserved in eukaryotes (Zhu et al, 2022) and that all TOR sequences analyzed have the DFG motif, this strategy can potentially be applied to other plants, or even to any other eukaryote by genome editing or by genetic transformation, as the resistance is conferred even in the presence of the WT alleles of TOR.…”

Section: Discussionmentioning

confidence: 99%

“…Although the phosphorylation of S6 kinases (S6K1 and S6K2) and their target the ribosomal protein S6 have been previously used to assess TOR activity, the plant community recently highlighted the need to develop alternative read‐outs of TOR activity (Henriques et al., 2022). During this study, we developed novel antibodies enabling the detection of the TOR‐dependent phosphorylation of YAK1, a direct TOR target (Forzani et al., 2019; Van Leene et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Highly selective inhibitors have been obtained for each PIKK, and pan‐PIKK inhibitors have also been developed (Chresta et al., 2010; Hsieh et al., 2012; Liu et al., 2013; Mao et al., 2022; Stakyte et al., 2021; Yu et al., 2010). While rapamycin is not efficient in wild type (WT) plants, potent ATP‐competitive TOR inhibitors have been used extensively in recent studies aiming to decipher the plant TOR signaling pathway but their selectivity were not yet fully adressed in plants (Henriques et al., 2022; Montané & Menand, 2019). We used the ATP‐competitive inhibitor AZD‐8055 for our pharmacogenetic screen because its selectivity to TOR (approx.…”

Section: Introductionmentioning

confidence: 99%

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A drug‐resistant mutation in plant target of rapamycin validates the specificity of ATP‐competitive TOR inhibitors in vivo

Perdoux,

Barrada,

Boulaiz

et al. 2023

The Plant Journal

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SUMMARYKinases are major components of cellular signaling pathways, regulating key cellular activities through phosphorylation. Kinase inhibitors are efficient tools for studying kinase targets and functions, however assessing their kinase specificity in vivo is essential. The identification of resistant kinase mutants has been proposed to be the most convincing approach to achieve this goal. Here, we address this issue in plants via a pharmacogenetic screen for mutants resistant to the ATP‐competitive TOR inhibitor AZD‐8055. The eukaryotic TOR (Target of Rapamycin) kinase is emerging as a major hub controlling growth responses in plants largely thanks to the use of ATP‐competitive inhibitors. We identified a dominant mutation in the DFG motif of the Arabidopsis TOR kinase domain that leads to very strong resistance to AZD‐8055. This resistance was characterized by measuring root growth, photosystem II (PSII) activity in leaves and phosphorylation of YAK1 (Yet Another Kinase 1) and RPS6 (Ribosomal protein S6), a direct and an indirect target of TOR respectively. Using other ATP‐competitive TOR inhibitors, we also show that the dominant mutation is particularly efficient for resistance to drugs structurally related to AZD‐8055. Altogether, this proof‐of‐concept study demonstrates that a pharmacogenetic screen in Arabidopsis can be used to successfully identify the target of a kinase inhibitor in vivo and therefore to demonstrate inhibitor specificity. Thanks to the conservation of kinase families in eukaryotes, and the possibility of creating amino acid substitutions by genome editing, this work has great potential for extending studies on the evolution of signaling pathways in eukaryotes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A drug‐resistant mutation in plant target of rapamycin validates the specificity of ATP‐competitive TOR inhibitors in vivo

Perdoux,

Barrada,

Boulaiz

et al. 2023

The Plant Journal

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“…Considering the ribosomal protein changes and the increase in root growth observed under

nutrition in maritime pine seedlings ( Ortigosa et al., 2020 ), it can be hypothesized a decrease of SnRK1 activity over the TOR complex in these conditions. The TOR complex integrates different developmental and environmental signals, including nutritional status, promoting ribosome biogenesis, translation, and plant growth ( Henriques et al., 2022 ). Finally, a transcript coding for a TCTP protein had several differential modifications ( Supplementary Dataset 11 ).…”

Section: Discussionmentioning

confidence: 99%

Epitranscriptome changes triggered by ammonium nutrition regulate the proteome response of maritime pine roots

et al. 2022

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Epitranscriptome constitutes a gene expression checkpoint in all living organisms. Nitrogen is an essential element for plant growth and development that influences gene expression at different levels such as epigenome, transcriptome, proteome, and metabolome. Therefore, our hypothesis is that changes in the epitranscriptome may regulate nitrogen metabolism. In this study, epitranscriptomic modifications caused by ammonium nutrition were monitored in maritime pine roots using Oxford Nanopore Technology. Transcriptomic responses mainly affected transcripts involved in nitrogen and carbon metabolism, defense, hormone synthesis/signaling, and translation. Global detection of epitranscriptomic marks was performed to evaluate this posttranscriptional mechanism in un/treated seedlings. Increased N6-methyladenosine (m6A) deposition in the 3’-UTR was observed in response to ammonium, which seems to be correlated with poly(A) lengths and changes in the relative abundance of the corresponding proteins. The results showed that m6A deposition and its dynamics seem to be important regulators of translation under ammonium nutrition. These findings suggest that protein translation is finely regulated through epitranscriptomic marks likely by changes in mRNA poly(A) length, transcript abundance and ribosome protein composition. An integration of multiomics data suggests that the epitranscriptome modulates responses to nutritional, developmental and environmental changes through buffering, filtering, and focusing the final products of gene expression.

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“…Initiation and modulation of autophagy in plants are under the tight control of both cellular energy censors, SnRK1 and TOR, whereby TOR itself is inhibited by SnRK1 when cellular re-arrangement is required. TOR activity inhibition is enhanced when environmental signals are additionally perceived and transmitted by SnRK2-dependent pathways ( Figure 2B ) ( Pu et al., 2017 ; Huang et al., 2019 ; Henriques et al., 2022 ). The complex interactions of SnRK1, SnRK2, TOR and autophagy that maintain cellular function under different growth conditions, which underpins plant growth and fitness, are currently intensively studied and will provide a better understanding of the environmental impact on plant productivity ( Hill et al., 2013 ; Barrada et al., 2015 ; Li et al., 2018 ; Ghatak et al., 2022a ; Kashkan et al., 2022 ).…”

Section: Evolutionary Conserved Cellular Sensors Coordinate Plant Str...mentioning

confidence: 99%

Recent insights into metabolic and signalling events of directional root growth regulation and its implications for sustainable crop production systems

Retzer

Weckwerth

2023

Front. Plant Sci.

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Roots are sensors evolved to simultaneously respond to manifold signals, which allow the plant to survive. Root growth responses, including the modulation of directional root growth, were shown to be differently regulated when the root is exposed to a combination of exogenous stimuli compared to an individual stress trigger. Several studies pointed especially to the impact of the negative phototropic response of roots, which interferes with the adaptation of directional root growth upon additional gravitropic, halotropic or mechanical triggers. This review will provide a general overview of known cellular, molecular and signalling mechanisms involved in directional root growth regulation upon exogenous stimuli. Furthermore, we summarise recent experimental approaches to dissect which root growth responses are regulated upon which individual trigger. Finally, we provide a general overview of how to implement the knowledge gained to improve plant breeding.

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Growing of the TOR world

Cited by 9 publications

References 49 publications

A drug‐resistant mutation in plant target of rapamycin validates the specificity of ATP‐competitive TOR inhibitors in vivo

A drug‐resistant mutation in plant target of rapamycin validates the specificity of ATP‐competitive TOR inhibitors in vivo

Epitranscriptome changes triggered by ammonium nutrition regulate the proteome response of maritime pine roots

Recent insights into metabolic and signalling events of directional root growth regulation and its implications for sustainable crop production systems

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