Novel links in the plant TOR kinase signaling network

doi:10.1016/j.pbi.2015.09.006

Current Opinion in Plant Biology

Volume 28, December 2015, Pages 83-91

https://doi.org/10.1016/j.pbi.2015.09.006 Get rights and content

Highlights

•
TOR integrates nutrient and energy signaling to promote cell division and growth.
•
Powerful chemical tools are developed for probing plant TOR functions.
•
Both conserved and unique TOR effectors are identified in the plant system.

Nutrient and energy sensing and signaling mechanisms constitute the most ancient and fundamental regulatory networks to control growth and development in all life forms. The target of rapamycin (TOR) protein kinase is modulated by diverse nutrient, energy, hormone and stress inputs and plays a central role in regulating cell proliferation, growth, metabolism and stress responses from yeasts to plants and animals. Recent chemical, genetic, genomic and metabolomic analyses have enabled significant progress toward molecular understanding of the TOR signaling network in multicellular plants. This review discusses the applications of new chemical tools to probe plant TOR functions and highlights recent findings and predictions on TOR-mediate biological processes. Special focus is placed on novel and evolutionarily conserved TOR kinase effectors as positive and negative signaling regulators that control transcription, translation and metabolism to support cell proliferation, growth and maintenance from embryogenesis to senescence in the plant system.

Introduction

The target of rapamycin (TOR) is an atypical serine-threonine protein kinase (PK) closely related to the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family conserved from yeasts to plants and humans. Extensive research over the past decade has demonstrated a pivotal role of TOR in sensing and responding to nutrient availability, cellular energy status, as well as stress and growth stimuli to drive cellular and organismal growth in all eukaryotes [1, 2, 3, 4, 5, 6•]. In photosynthetic organisms from unicellular Chlamydomonas reinhardtii to flowering plants, TOR has emerged as a central integrator of nutrient, energy and stress signaling networks [4, 6•, 7, 8•]. Recent studies have also led to new links for TOR-regulated translational reinitiation of specific mRNAs stimulated by auxin [9^••] and viral infection [10].

How TOR kinase modulates a broad spectrum of cellular processes from transcription, translation to metabolic reprogramming to support cell proliferation and growth has been the focus of intensive research. In the budding yeast Saccharomyces cerevisiae, Sch9 (an AGC family kinase and ortholog of plant and mammalian small ribosome protein S6 kinase, S6K), Tap42 (a regulator of PP2A phosphatases and ortholog of plant type 2A-phosphatase-accociated protein 46 kDa, TAP46), and Atg1 (an ortholog of plant and mammalian autophagy related kinase, ATG1/ULK1) are three direct effectors of TOR complex 1 (TORC1) that act as master regulators of transcription, protein synthesis and autophagy [3, 11, 12]. More elaborate TOR signaling networks are emerging in multicellular animals and plants. Current knowledge indicates that mammalian TORC1 phosphorylates S6K, 4E-BP (eukaryotic translation initiation factor 4E binding protein), GRB10 (growth factor receptor-bound protein 10), LIPIN and ATG1/ULK1 to control directly translation and autophagy, but indirectly transcription [5]. Whereas mammalian TORC2 could phosphorylate AKT to regulate cytoskeleton structure, glycolysis, glycogenesis, and lipogenesis, there is no evidence to support the presence and function of TORC2 in plants yet [6^•]. Although the phosphorylation and regulation of S6K, TAP46, LIPIN and ATG1 by plant TOR kinase may share some functional and mechanistic conservation as those in the budding yeast and mammals, recent discoveries have identified previously unknown TOR substrates and regulatory mechanisms in transcription, as well as ribosome biogenesis and translational controls crucial to plant cell proliferation and growth regulation. Comprehensive review articles have summarized recent studies of Arabidopsis tor and related mutants [13••, 14, 15, 16••], which unravel the multifaceted roles of TOR signaling in plant growth, metabolism and senescence [4, 6•, 17, 18]. This review highlights the latest progress on applying chemical and genetic perturbations to identify novel molecular links and elucidate regulatory mechanisms in the plant TOR signaling network.

Section snippets

Exploring chemical tools to uncover diverse TOR functions

The characterization of many tor null mutants confirms that TOR deficiency results in early embryo arrest and lethality in Arabidopsis (Figure 1), which supports its essential role in plant growth and development but hindered the investigation of more TOR functions and regulatory mechanisms [19, 20]. Although green alga C. reinhardtii is sensitive to rapamycin at 500 nM [21, 22, 7], early studies suggested that flowering plants were insensitive to rapamycin and the FKBP-rapamycin-binding domain

TOR regulators and effectors

How TOR kinase senses diverse upstream regulatory signals and controls a myriad of direct or indirect downstream effectors to modulate cellular, metabolic and physiological processes are the most fascinating questions in understanding the plant TOR signaling network (Figure 3). Glucose and sucrose derived from photosynthesis stimulated by light and CO₂ appear to be the most effective nutrient signals to activate plant TOR kinase [15, 16••]. Glucose metabolism through glycolysis and

Ribosome biogenesis and translational control

The most conserved functions of TOR signaling are to promote ribosome biogenesis and translation in yeast, plants and mammals in response to nutrients and growth regulators [3, 4, 5, 6•]. Consistently, glucose-TOR signaling activates more than 100 primary target genes encoding ribosomal proteins (RPS and RPL), ribosomal RNA processing proteins, ribosome biogenesis regulatory protein, and protein initiation and elongation factors in Arabidopsis [14, 16••]. Interestingly, these genes are also

Cell cycle and cell size regulation

Rapamycin arrested yeast and mammalian cells in the G1 phase of cell cycle. Arabidopsis null tor mutants were arrested during early embryogenesis and prevented postembryonic seedling development. The precise molecular mechanisms controlling the cell cycle by TOR signaling remained mostly unknown for decades [3, 4, 5, 15, 24]. Genome-wide analyses of early glucose-TOR signaling target genes in WT and inducible null tor plants have provided clear evidence that Arabidopsis TORC1 is directly

Future challenges

The biological functions of plant TOR in embryogenesis, seedling and plant growth, metabolism, and senescence have emerged. The molecular regulatory mechanisms of the plant TOR signaling network are starting to be elucidated in the root meristems and growing and differentiated cells. The application of versatile chemical tools and integrated systems, cellular, genetic, genomic and phosphoproteomic analyses will facilitate the discoveries of new regulators and molecular links in TOR signaling.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

We apologize for limited literature coverage due to space limitation. The projects on the plant TOR signaling network have been supported by the NIH grants and WJC Special Project RDA-Korea to J.S. Y.X. is supported by Chinese Academy of Sciences.

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Cited by (107)

TOR in plants: Multidimensional regulators of plant growth and signaling pathways
2024, Journal of Plant Physiology
Target Of Rapamycin (TOR) represents a ubiquitous kinase complex that has emerged as a central regulator of cell growth and metabolism in nearly all eukaryotic organisms. TOR is an evolutionarily conserved protein kinase, functioning as a central signaling hub that integrates diverse internal and external cues to regulate a multitude of biological processes. These processes collectively exert significant influence on plant growth, development, nutrient assimilation, photosynthesis, fruit ripening, and interactions with microorganisms. Within the plant domain, the TOR complex comprises three integral components: TOR, RAPTOR, and LST8.
This comprehensive review provides insights into various facets of the TOR protein, encompassing its origin, structure, function, and the regulatory and signaling pathways operative in photosynthetic organisms. Additionally, we explore future perspectives related to this pivotal protein kinase.
Phosphoproteomics analysis of the effect of target of rapamycin kinase inhibition on Cucumis sativus in response to Podosphaera xanthii
2023, Plant Physiology and Biochemistry
Target of rapamycin (TOR) kinase is a conserved sensor of cell growth in yeasts, plants, and mammals. Despite the extensive research on the TOR complex in various biological processes, large-scale phosphoproteomics analysis of TOR phosphorylation events upon environmental stress are scarce. Powdery mildew caused by Podosphaera xanthii poses a major threat to the quality and yield of cucumber (Cucumis sativus L.). Previous studies concluded that TOR participated in abiotic and biotic stress responses. Hence, studying the underlying mechanism of TOR-P. xanthii infection is particularly important. In this study, we performed a quantitative phosphoproteomics studies of Cucumis against P. xanthii attack under AZD-8055 (TOR inhibitor) pretreatment. A total of 3384 phosphopeptides were identified from the 1699 phosphoproteins. The Motif-X analysis showed high sensitivity and specificity of serine sites under AZD-8055-treatment or P. xanthii stress, and TOR exhibited a unique preference for proline at +1 position and glycine at −1 position to enhance the phosphorylation response to P. xanthii. The functional analysis suggested that the unique responses were attributed to proteins related to plant hormone signaling, mitogen-activated protein kinase cascade signaling, phosphatidylinositol signaling system, and circadian rhythm; and calcium signaling– and defense response–related proteins. Our results provided rich resources for understanding the molecular mechanism of how the TOR kinase controlled plant growth and stress adaptation.
Effects of fishmeal replacement by Clostridium autoethanogenum protein on the growth, digestibility, serum free amino acid and gene expression related to protein metabolism of obscure pufferfish (Takifugu obscurus)
2022, Animal Feed Science and Technology
Citation Excerpt :
Thus, more studies will be necessary to investigate the effect of fishmeal replacement by CAP on gene expression related to amino acid transporters in intestine. The target of rapamycin (TOR), a serine/threonine kinase, can mediate the synthesis of protein by enhancing the activity of S6 kinase 1 (S6K1) and depressing the activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (Ma and Blenis, 2009; Xiong and Sheen, 2016). In the present study, we found that fishmeal replaced by CAP significantly up-regulated the expression of TOR in muscle but had no significant differences on the S6K1 and 4E-BPs mRNA levels in muscle and liver among treatments.
A 63-day feeding trial was conducted to evaluate the effect of Clostridium autoethanogenum protein (CAP) on the growth, digestibility, postprandial free amino acid concentrations in serum, and gene expression related to protein metabolism in obscure pufferfish (Takifugu obscurus). The basal diet with 420 g/kg of fishmeal was used as the control diet (CAP0), and then 20 % (CAP20), 40 % (CAP40) and 80 % (CAP80) dietary fishmeal were replaced by CAP. Compared with diet CAP0, the growth and feed utilization was not affected in fish fed diet CAP20, but was significantly reduced in fish fed diets CAP40 and CAP80 (P < 0.05). The apparent digestibility coefficients (ADCs) of dry matter and protein in the CAP80 group were significantly lower (P < 0.05) than those of the other three groups, and the ADC of lipid was significantly decreased (P < 0.05) in the CAP40 and CAP80 groups. Fish fed diets CAP40 and CAP80 had lower taurine content in muscle compared to those fed diets CAP0 and CAP20 (P < 0.05). Higher free essential amino acid concentrations in serum were observed in fish fed diet CAP80 compared to the other diets at 2 h after refeeding (P < 0.05). Fish fed diets CAP40 and CAP80 showed lower hardness and gumminess in muscle than those fed the other diets (P < 0.05). The expression of peptide transporter1 (PepT1) in intestine and target of rapamycin (TOR) in muscle were significantly up-regulated in the CAP40 groups compared to the control (CAP0) (P < 0.05). However, relative expressions of 4F2 heavy chain (4F2hC), L-type amino acid transporter 2 (y⁺LAT2) and T-type amino acid transporter1(TAT1) in intestine were not significantly affected by graded levels of CAP (P > 0.05). The inclusion of CAP did not significantly affect the expression of ribosomal protein S6 kinase 1 (S6K1), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and 4E-BP2 (P > 0.05) in muscle and liver. In summary, in a basal diet containing 420 g/kg fishmeal, 20 % fishmeal in diets could be successfully substituted by CAP, while high-level CAP decreased the growth, feed utilization and digestibility in juvenile obscure pufferfish. The main reasons for the inhibition of growth performance were probably that excessive CAP caused dietary taurine deficiency and the imbalance of amino acid absorption.
Early signaling events in the heat stress response of Pyropia haitanensis revealed by phosphoproteomic and lipidomic analyses
2022, Algal Research
Deciphering the heat stress signaling pathway will increase our ability to improve the thermotolerance of the economically important seaweed species Pyropia haitanensis, as one component of sustainable development against a background of ongoing climate change. Protein phosphorylation has several functions, including the integration of various signals, gene expression, and metabolic activities, in plant responses to abiotic stresses. In this study, we used quantitative phosphoproteomics and lipidomics techniques to identify the putative signal and downstream responses involved in P. haitanensis thermotolerance. The results revealed a broad network of highly dynamic changes in the phosphoprotein profile of thalli exposed to heat stress. The functional annotation of differentially phosphorylated proteins indicated that many of them are involved in calcium signaling, target of rapamycin (TOR) signaling, and mitogen-activated protein kinase (MAPK) signaling pathways at 30 min and 6 h under heat stress. Differentially phosphorylated proteins involved in phosphatidylinositol signaling, energy metabolism, and endocytosis as well as heat shock proteins were enriched at 12, 18, and 24 h after the heat treatment was initiated. Further analyses suggested that Ca²⁺ signaling and MAPK signaling may regulate the early response of thalli to heat stress by activating heat shock proteins. TOR signaling may lead to the rapid phosphorylation of the translation initiation factor to promote protein synthesis and trigger glycolysis to provide the energy and intermediate metabolites needed for thalli to resist the adverse effects of heat stress. Additionally, PI signaling was activated later to regulate the removal of polyunsaturated monogalactosyldiacylglycerol, increase saturated triacylglycerol contents, and increase endocytosis to maintain thalli membrane integrity in response to sustained heat stress. The present data provide insights into the signaling networks involved in the P. haitanensis response to heat stress.
Roles of TOR signaling in nutrient deprivation and abiotic stress
2022, Journal of Plant Physiology
In living organisms, nutrient, energy, and environmental stimuli sensing and signaling are considered as the most primordial regulatory networks governing growth and development. Target of Rapamycin (TOR) is a diversified Serine/Threonine protein kinase existing in all eukaryotes that regulates distinct salient growth and developmental signaling pathways. TOR signaling acts as a central hub in plants that allows a variety of nutrients, energy, hormones, and environmental stimuli to be integrated. TOR is activated by several nutrients and promotes energy-consuming processes such as cell division, protein translation, mRNA translation and ribosome biogenesis. We summarized the recent findings on the TOR function in regulating the dynamic networks of nutrients, including sugar, sulfur, nitrogen, carbon, phosphorus, potassium, and amino acids. TOR's role in abiotic stress was discussed, in which TOR orchestrating stress signaling, including heat, cold, salt, and osmotic stress, to regulate transcriptional and metabolic reprogramming, as well as growth and development. The interconnections between TOR and SnRK1 kinase were discussed in controlling nutrient deprivation and abiotic stress.
VvMYB1 potentially affects VvTOR gene expression by regulating VvTOR promoter and participates in glucose accumulation
2022, Journal of Plant Physiology
MYB (v-myb avian myeloblastosis viral oncogene homolog) transcription factors make up one of the largest protein families in plants. The TOR (target of rapamycin) signaling network plays a pivotal role in sugar metabolism and plant growth. In this article, we utilized grape (Vitis vinifera) calli to explore the relationship between VvMYB1 and VvTOR. By using yeast one-hybrid and dual-luciferase reporter system, we speculated that there may be other proteins that help VvMYB1 and VvTOR promoter bond in grape calli, and the interaction action sites were located between the VvTOR 400-bp promoter fragment and the 1200-bp promoter fragment. The subcellular localization results suggest that VvMYB1 is found in the nucleus. Moreover, the expression level of VvTOR increased in the transgenic calli with overexpression of VvMYB1. These findings provide further evidence that VvMYB1 regulates VvTOR expression. We also found that overexpression of VvMYB1 increased glucose accumulation and affected expression of sugar-related genes. Our results suggest that there is a crosstalk between VvMYB1, VvTOR, and glucose accumulation.

View all citing articles on Scopus

View full text

Novel links in the plant TOR kinase signaling network

Highlights

Introduction

Section snippets

Exploring chemical tools to uncover diverse TOR functions

TOR regulators and effectors

Ribosome biogenesis and translational control

Cell cycle and cell size regulation

Future challenges

References and recommended reading

Acknowledgements

Curr Opin Plant Biol

Plant Physiol

Mol Cell

Mol Cells

Science

Nature

J Gen Virol

EMBO J

Transcriptional regulation of the stress response by mTOR

Sci Signal

AMPK: positive and negative regulation, and its role in whole-body energy homeostasis

Curr Opin Cell Biol

Target of rapamycin (TOR) in nutrient signaling and growth control

Genetics

Making new contacts: the mTOR network in metabolism and signalling crosstalk

Nat Rev Mol Cell Biol

The role of target of rapamycin signaling networks in plant growth and metabolism

Plant Physiol

Inhibition of target of rapamycin signaling and stress activate autophagy in Chlamydomonas reinhardtii

Plant Physiol

Master regulators in plant glucose signaling networks

J Plant Biol

TOR and S6K1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF3h

EMBO J

Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation

EMBO J

Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis

Genes Dev

Dynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis

Sci Signal

Systemic analysis of inducible target of rapamycin mutants reveal a general metabolic switch controlling growth in Arabidopsis thaliana

Plant J

Mutations in the Arabidopsis homolog of LST8/GbetaL, a partner of the target of Rapamycin kinase, impair plant growth, flowering, and metabolic adaptation to long days

Plant Cell

Target of rapamycin signaling regulates metabolism, growth, and life span in Arabidopsis

Plant Cell

Glucose-TOR signalling reprograms the transcriptome and activates meristems

Nature

Balancing act: matching growth with environment by the TOR signalling pathway

J Exp Bot

Sugar metabolism and the plant target of rapamycin kinase: a sweet operaTOR?

Front Plant Sci

Expression and disruption of the Arabidopsis TOR (target of rapamycin) gene

Proc Natl Acad Sci U S A

Target of rapamycin regulates development and ribosomal RNA expression through kinase domain in Arabidopsis

Plant Physiol

Inhibition of target of rapamycin signaling by rapamycin in the unicellular green alga Chlamydomonas reinhardtii

Plant Physiol

Metabolomic response of Chlamydomonas reinhardtii to the inhibition of target of rapamycin (TOR) by rapamycin

J Microbiol Biotechnol

Arabidopsis TARGET OF RAPAMYCIN interacts with RAPTOR, which regulates the activity of S6 kinase in response to osmotic stress signals

Plant Cell