Dynamic Nutrient Signaling Networks in Plants

Abstract

Nutrients are vital to life through intertwined sensing, signaling, and metabolic processes. Emerging research focuses on how distinct nutrient signaling networks integrate and coordinate gene expression, metabolism, growth, and survival. We review the multifaceted roles of sugars, nitrate, and phosphate as essential plant nutrients in controlling complex molecular and cellular mechanisms of dynamic signaling networks. Key advances in central sugar and energy signaling mechanisms mediated by the evolutionarily conserved master regulators HEXOKINASE1 (HXK1), TARGET OF RAPAMYCIN (TOR), and SNF1-RELATED PROTEIN KINASE1 (SNRK1) are discussed. Significant progress in primary nitrate sensing, calcium signaling, transcriptome analysis, and root-shoot communication to shape plant biomass and architecture are elaborated. Discoveries on intracellular and extracellular phosphate signaling and the intimate connections with nitrate and sugar signaling are examined. This review highlights the dynamic nutrient, energy, growth, and stress signaling networks that orchestrate systemwide transcriptional, translational, and metabolic reprogramming, modulate growth and developmental programs, and respond to environmental cues.

Keywords: HEXOKINASE1; HXK1; SNF1-RELATED PROTEIN KINASE1; SNRK1; TARGET OF RAPAMYCIN; TOR; glucose signaling; nitrate signaling; phosphate signaling.

Figure 1

Carbon, nitrogen, and phosphorus are essential nutrients that control integrated signaling networks in plants. (a) Sugars are generated by photosynthesis from source leaves and translocated to sink organs. Nitrate (NO ⁻₃) and phosphate (PO ^3-₄) are acquired by roots from the soil and transported to shoots. (b) Glucose-sensor HXK1 and energy sensors TOR and SNRK1 respond to different concentrations of sugars. NRT1.1 is a nitrate transceptor and mediates nitrate-activated CPK-NLP signaling to induced PNRs. Phosphate is taken up by PHT1 and converted to InsP₈, which is sensed by SPX to repress PHR1 in PSRs. Other TFs also regulate PNR and PSR. (c) ❶ (Top) HXK1-mediated growth promotion in adult Arabidopsis plants and (bottom) growth arrest in seedlings on high glucose in WT and hxk1 plants. ❷ WT, snrk1, and SNRK1-OX plants. ❸ WT and conditional tor seedlings. ❹ Seedlings supplied with KCl (control) and different nitrogen sources, NH₄⁺, Gln, and NO₃⁻. ❺ Seedlings grown in the medium with (+) or without (−) Phosphate (Pi). Abbreviations: CPK, CALCIUM DEPENDENT PROTEIN KINASE; Glc, glucose; Gln, glutamine; HXK1, HEXOKINASE1; InsP₈, inositol phyrophosphate; NLP, NIN-LIKE PROTEIN; OX, overexpression; P, phosphorylation; PHR1, PHOSPHATE STARVATION RESPONSE1; PHT1, PHOSPHATE TRANSPORTER1; PNR, primary nitrate response; PSR, phosphate-starvation response; SNRK1, SNF1-RELATED PROTEIN KINASE1; SPX, SYG1/Pho81/XPR1; T6P, trehalose 6-phosphate; TF, transcription factor; TOR, TARGET OF RAPAMYCIN; WT, wild type.

Figure 2

Sugar sensing and signaling in plants. Glucose sensor HXK1 controls multiple biological processes at different glucose concentrations uncoupled from metabolism. Sucrose and glucose metabolism generate diverse sugars and metabolites that could potentially be perceived by distinct sensors. Abbreviations: Acetyl CoA, acetyl coenzyme A; FBP, fructose-1,6-bisphosphatase; G1P, glucose 1-phosphate; G6P, glucose 6-phosphate; Gln, glutamine; GlcNAc, N-acetylglucosamine; HXK, HEXOKINASE; INV, invertase; OGT, O-LINKED N-ACETYLGLUCOSAMINE (O-GLcNAc) TRANSFERASE; R5P, ribose 5-phosphate; RGS1, REGULATOR OF G-PROTEIN SIGNALING1; SNRK1, SNF-RELATED PROTEIN KINASE1; SUS, SUCROSE SYNTHASE; T6P, trehalose 6-phosphate; TOR, TARGET OF RAPAMYCIN; TPP, T6P PHOSPHATASE; TPS, T6P SYNTHASE; UDP, uridine diphosphate.

Figure 3

TOR acts as a central hub to integrate nutrient, energy, and environmental cues to orchestrate growth and development. The TOR complex is composed of TOR, RAPTOR, and LST8 and is promoted by the ATPase cochaperone complex TTT-WAC-RUVBL for dimerization and activation. ATP generated from the mitochondrial ETC, glucose, light, nutrients (N, P, or S), and amino acids promotes TOR activation. TOR phosphorylation of substrates (with orange circled Ps) activates (orange text) or represses (blue text) their functions in various biological processes. RPS6 KINASE (S6K) can also phosphorylate targets (with grey circled Ps). TOR is inhibited by SNRK1 and ABA. TOR phosphorylates and inhibits the ABA receptor PYL. Reciprocally, the ABA-PYL-SNRK2 cascade inhibits TOR activity through RAPTOR phosphorylation. Abbreviations: ABA, abscisic acid; ATG, AUTOPHAGY-RELATED; BIN2, BRASSINOSTEROID INSENSITIVE2; BR, brassinosteroid; COP1, CONSTITUTIVELY PHOTOMORPHOGENIC1; E2F, E2 TRANSCRIPTION FACTOR; EIF3h, EUKARYOTIC INITIATION FACTOR 3h; ETC, electron transport chain; G6P, glucose 6-phosphate; HXK, HEXOKINASE; LARP1, LA-RELATED PROTEIN1; LST8, LETHAL-WITH-SEC13-PROTEIN8; MRF1, MA3-DOMAIN-CONTAINING-TRANSLATION-REGULATORY-FACTOR1; PP2C, PROTEIN PHOSPHATASE 2C; PYL, PYRABACTIN RESISTANCE-LIKE; RAPTOR, REGULATORY-ASSOCIATED-PROTEIN-OF-MTOR1; ROP2, RHO-OF-PLANTS2; RPS6, RIBOSOMAL PROTEIN S6; RUVBL, RUVB-LIKE AAA ATPASE1; SNRK, SNF1-RELATED PROTEIN KINASE; TAP46, 2A PHOSPHATASE ASSOCIATED PROTEIN OF 46 KD; TOR, TARGET OF RAPAMYCIN; TTT, TEL2-TTI1-TTI2; WAC, WWDOMAIN CONTAINING ADAPTOR WITH COILED-COIL; YAK1, YET ANOTHER KINASE1.

Figure 4

SNRK1 plays a central role in sensing nutrient deprivation and stress to promote catabolism but inhibit anabolism and growth. The SNRK1 complex is composed of catalytic a (KIN10/11) and regulatory β and βγ subunits. SNRK1 is activated by darkness, stress, starvation, hypoxia, and SNAKs but inhibited by sugars, metabolites, and FLZ repressors. SNRK1 phosphorylation positively (orange text) or negatively (blue text) regulates targets in broad biological processes. The catalytic a subunits (KIN10/11) can translocate to the nucleus to phosphorylate various TFs. KIN10 represses EIN3, MYC2, WRI1, IDD8, and PIF4 but activates FUS3, bZIP63, and SPCH. SNRK1 also phosphorylates and inhibits cytosolic enzymes, including SPS, NR, TPS7/8/9, and HMGR; translation regulators ISO4E, ISO4G, and ELF4E; and other signaling proteins in various biological responses. SNRK1 antagonizes TOR complex signaling by phosphorylating RAPTOR. Abbreviations: ABA, abscisic acid; ABI1, ABA INSENSITIVE1; ATG1, AUTOPHAGY RELATED1; bZIP, BASIC LEUCINE ZIPPER; EIN3, ETHYLENE INSENSITIVE3; ELF4E, EUKARYOTIC TRANSLATION INITIATION FACTOR 4E; F2KP, fructose-2,6-bisphosphatase; FLZ, FCS-LIKE ZINC FINGER; FUS3, FUSCA3; G1P, glucose 1-phosphate; G6P, glucose 6-phosphate; HMGR, 3-HYDOXY-3-METHYLGLUTARYL–COA REDUCTASE; IDD8, INDETERMINATE DOMAIN8; KIN10/11, KINASE10/11; MPK, MITOGEN-ACTIVATED PROTEIN KINASE; NR, NITRATE REDUCTASE; P, phosphorylation; PIF4, PHYTOCHROME INTERACTING FACTOR4; PP2CA, PROTEIN PHOSPHATASE 2CA; PTP, PROTEIN TYROSINE PHOSPHATASE; RAPTOR, REGULATORY-ASSOCIATED-PROTEIN-OF-MTOR1; SNAK, SNRK1-ACTIVATING KINASE; SNRK1, SNF1-RELATED KINASE1; SPCH, SPEECHLESS; SPS, SUCROSE PHOSPHATE SYNTHASE; T6P, trehalose 6-phosphate; TF, transcription factor; TOR, TARGET OF RAPAMYCIN; TPS, T6P SYNTHASE; UDP, uridine diphosphate; WRI1, WRINKLED1.

Figure 5

The nitrate sensing and signaling network. Nitrate triggers the nuclear Ca²⁺-CPK-NLP6/7 cascade and induces genes encoding activators (orange text) and repressors (blue text) of the PNRs. Nitrate-activated genes encoding TFs, including NIGT1s and LBD37/38/39, repress N-starvation genes. Nitrate activates the synthesis and signaling of the plant hormones cytokinin and auxin but degrades ABA. The activity of the nitrate transceptor NRT1.1 is regulated by CBL1/9-CIPK23, which is inhibited by ABI2/PP2C. Nitrogen starvation activates the CLE1/3/4/7 peptides to repress lateral root development and triggers CEPs to move to the shoot to activate CEPRs. Activated CEPD1/2 proteins in the shoot then translocate to the root to enhance nitrate uptake. Abbreviations: ABA, abscisic acid; ABI2, ABA INSENSITIVE2; AFB, AUXIN-SIGNALING F-BOX; ANR, ARABIDOPSIS NITRATE REGULATED1; CBL, CALCINEURIN B-LIKE; CEP, C-TERMINALLY ENCODED PEPTIDE; CEPD, CEP DOWNSTREAM; CEPR; CEP RECEPTOR; CIPK, CBL-INTERACTING PROTEIN KINASE; CLE, CLAVATA3/EMBRYO SURROUNDING REGION-RELATED; CPK, CALCIUM DEPENDENT PROTEIN KINASE; CRF, CYTOKININ-RESPONSE FACTOR; CYP, cytochrome P450; IPT3, ISOPENTENYLTRANSFERASE3; LBD, LATERAL ORGAN BOUNDARIES DOMAIN; NAC, NAM, ATAF, CUC; NIGT1, NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR1; NLP, NIN-LIKE PROTEIN; NRT1.1, NITRATE TRANSPORTER 1.1; PNR, primary nitrate response; PP2C, PROTEIN PHOSPHATASE2C; TAR, TRYPTOPHAN AMINOTRANSFERASE RELATED; TCP, TEOSINTE BRANCHED 1/CINCINNATA/PROLIFERATING CELL FACTOR; TF, transcription factor; TGA, TGACG SEQUENCE-SPECIFIC BINDING PROTEIN1.

Figure 6

(a) PSRs in shoots and roots. P_i is taken up by PHT1 transporters and converted to the signaling molecule InsP₈, which is perceived by the SPX sensor to inhibit PHR1. Under P_i starvation, the key TFs PHR1/PHL induce transcriptome reprogramming to promote PSRs in both shoots and roots as well as shoot-to-root mobile mRNAs and miRNA. Shoot miR399 inhibits root PHO2, encoding a ubiquitin E2 conjugase for the degradation of PHT1 and PHO1 transporters. In roots, low external P_i induces iron-dependent ROS by derepressing ferroxidase LPR1/2 and promoting nuclear TF STOP1 to enhance malate transporter ALMT1. Activated CLE14 peptide inhibits the key TFs SHR/SCR and WOX5 as well as auxin transporter PINs and arrests the primary root meristem. Root PSRs also induce the hormones auxin and cytokinin to promote lateral root and root hair growth. (b) High N levels promote PSRs by multiple mechanisms. Nitrate enhances TF PHR1 by stabilizing the protein and degrading the SPX repressor. The nitrate-NRT1.1-CPK-NLP cascade or the nitrate-NRT1.1-NBIP-SPX-NLP relay activates NIGT1s to repress SPXs and PHO2 encoding repressors of the PSR but activates PHT1s to enhance P_i uptake. Nitrate also enhances the PSR by a PHO2-dependent mechanism independent of PHR1. Abbreviations: ALMT1, ALUMINUM-ACTIVATED MALATE TRANSPORTER1; ALS3, ALUMINUM SENSITIVE3; AUX1, AUXIN TRANSPORTER PROTEIN1; CLE14, CLAVATA3/ESR-RELATED14; CPK, CALCIUM-DEPENDENT PROTEIN KINASE; ER, endoplasmic reticulum; InsP₈, inositol pyrophosphate8; LHW, LONESOME HIGHWAY; LPR, LOW PHOSPHATE ROOT; miRNA, microRNA; mRNA, messenger RNA; NBIP, NRT1.1B INTERACTING PROTEIN; NIGT1, NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR1; NLA, NITROGEN LIMITATION ADAPTATION; NLP, NIN-LIKE PROTEIN; NRT1.1, NITRATE TRANSPORTER 1.1; P, phosphorylation; PDR2, PHOSPHATE DEFICIENCY RESPONSE2; PHF1, PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1; PHL, PHR1-LIKE; PHO, PHOSPHATE; PHR, PHOSPHATE STARVATION RESPONSE1; PHT1, PHOSPHATE TRANSPORTER1; P_i, phosphate; PIN, PIN-FORMED; PSR, phosphate-starvation response; ROS, reactive oxygen species; SCR, SCARECROW; SHR, SHORT-ROOT; SPX, SYG1/Pho81/XPR1; STAR1, SENSITIVE TO ALUMINUM RHIZOTOXICITY1; STOP1, SENSITIVE TO PROTON TOXICITY1; TF, transcription factor; TIR1, TRANSPORT INHIBITOR RESPONSE1; TMO5, TARGET OF MONOPTEROS5; Ub, ubiquitination; VIH, VIP-HOMOLOG; WOX5, WUSCHEL RELATED HOMEOBOX5.