NRT1.1 was first characterised as a low-affinity nitrate transporter (LAT), as disruption of NRT1.1 function in nrt1.1 mutants led to a >80% decrease in nitrate uptake in sufficient nitrate (25mm KNO₃) growth medium compared with that of the wild-type plants (Huang et al., 1996). Consistent with this result, a recent study by Ye et al. (2019) reported that the nrt1.1 mutants showed approximately 50% less nitrate uptake than the wild type under 4mm nitrate conditions, indicating that the contribution of LATS of NRT1.1 at high nitrate supply was at least 50%. However, when nitrate levels were below 0.25mm, NRT1.1 was shown to act as a high-affinity nitrate transporter (HAT) and NRT1.1 was demonstrated to be responsible for approximately 75% of HATS in Arabidopsis (Liu et al., 1999). Subsequent analysis of nitrate uptake activity in plants and Xenopus oocytes revealed that NRT1.1 has a biphasic nitrate uptake kinetic feature, in which the affinity switch is regulated by the phosphorylation on the T101 residue of the NRT1.1 protein (Liu and Tsay, 2003; Rashid et al., 2018), and these findings provided the underlying operating mechanism of NRT1.1 dual-affinity activity. Notably, investigators in some later studies questioned the contribution of the HATS of NRT1.1 to nitrate uptake under low nitrate conditions (Glass and Kotur, 2013; Noguero et al., 2018); for example, functional disruption of NRT2.1 in plants resulted in a 96% reduction in the HATS influx of nitrate (Yong et al., 2010; Kotur et al., 2012), indicating that the contribution of the HATS of NRT1.1 at low nitrate supply was <4% of the wild-type uptake. Intriguingly, Ye et al. (2019) recently re-evaluated the role of NRT1.1 in nitrate uptake in Arabidopsis under low nitrate supply by generating a nrt1.1/2.1/2.2 triple mutant that could eliminate the contributions of NRT2.1 and NRT2.2 on the HATS influx of nitrate. The nrt1.1/2.1/2.2 triple mutant was found to have greater growth arrest and a lower rate of nitrate uptake than the nrt2.1/2.2 double mutants in 0.2mm nitrate growth medium, suggesting that NRT1.1-mediated HATS is necessary for plant growth under low nitrate growth conditions. By subtracting the root nitrate uptake rate of the nrt1.1/2.1/2.2 mutants from those of the nrt2.1/2.2 mutants, the authors proposed that ~12% of the high-affinity nitrate uptake in plants was attributed to NRT1.1 in 0.2mm nitrate growth medium (Ye et al., 2019). Therefore, NRT1.1 is indispensable for maintaining plant growth under both high- and low nitrate growth conditions.

With the aim of further illustrating how T101 phosphorylation switches the transport affinity of NRT1.1, researchers in two independent studies revealed the crystal structure of Arabidopsis NRT1.1, suggesting a potential structural significance for phosphorylation (Parker and Newstead, 2014; Sun et al., 2014). The NRT1.1 protein crystallises with two monomers (A and B) in each asymmetric unit which are almost identical to each other and adopt the canonical major facilitator superfamily fold. Each monomer is comprised of 12 transmembrane spanning alpha helices (TMHs) that form a clearly defined cavity that opens towards the cytoplasmic side (Sun and Zheng, 2015; Rashid et al., 2019), within which the substrate can bind. Therefore, unmodified NRT1.1 has an inward-facing conformational state. In the crystal, the phosphorylation site, T101, is located at the N-terminal end of one TMH and is entirely buried in a hydrophobic pocket that is directly adjacent to the dimer interface. Based on data from several analyses, Sun et al. (2014) proposed that NRT1.1 adopts a dimer configuration and functions as a low-affinity transporter, whereas phosphorylated NRT1.1 undergoes dimer decoupling and shows a high-affinity state. How the dimeric switch regulates the Michaelis constant (Km) of NRT1.1 remains unknown.

In addition to decoupling the dimer, phosphorylation of T101 can alter the localised structural properties of the dimer (Parker and Newstead, 2014). To investigate the function of T101 phosphorylation, Parker and Newstead generated a Thr101Asp mutant, which can mimic permanent phosphorylation of NRT1.1. As predicted, the Thr101Asp mutant, as NRT1.1-101D, showed a lower melting temperature, indicating enhanced structural flexibility compared to the NRT1.1 protein of the wild type. Meanwhile, the nitrate transport rate of the Thr101Asp mutant was higher than that of the wild-type protein based on the liposome-based uptake assay. Thus, T101 phosphorylation increases the nitrate transport rate, which may result from the enhanced structural flexibility of the NRT1.1 protein. The seemingly contrasting conclusions of the two studies can, however, be reconciled—phosphorylation on T101 induces dimer decoupling, which might increase structural flexibility, thereby converting the low-affinity state of NRT1.1 to a high-affinity state (Figure 1; Tsay, 2014; Rashid et al., 2018).

A key question for the working mechanism of NRT1.1 is how can nitrate be recognised? The aforementioned studies on the NRT1.1 crystal implied that His356 is an important structural element for nitrate binding of NRT1.1, which was demonstrated by mutagenesis studies where H356A abolished nitrate uptake activity of NRT1.1 at high and low nitrate concentrations (Sun et al., 2014; Wen and Kaiser, 2018). Consistent with this finding, Rashid et al. (2018) carefully compared the nitrate-binding pocket composition of two monomers (A and B) in apo- and nitrate-bound crystal structures of NRT1.1, noting that nitrate binds to His356 and Thr360 through H-bonding in monomer A, and to His356 and Arg45 in monomer B. Compared with the apo-protein structure, in the nitrate-bounded protein structure, the T101 neighbourhood composition in monomer A differs by the residues Ala106 and Val163, and in protomer B, the composition differs by the residues Ala165. Furthermore, Ramachandran plot and electron density maps for NRT1.1 apo- and nitrate-bound protein showed that nitrate binding triggers large conformational changes of both the nitrate-binding residues and phosphorylation sites T101, enhancing asymmetries between the monomers, which bring a functional consequence that the affinity of monomer A has almost a 5-fold higher affinity than monomer B, indicating their differential roles in the nitrate binding of NRT1.1 (Pires and Ascher, 2016; Rashid et al., 2018). Further rigidity analysis of protein structure found that nitrate binding triggers more changes in chemical interactions in monomer A, resulting in the redistribution of rigid clusters of atoms, which form the largest rigid cluster (LRC) and interlink the nitrate-binding pocket and the phosphorylation site residues (Rashid et al., 2018, 2019). Such a rigid cluster has not been predicted in protomer B, indicating weak or absent allosteric communication between the binding and T101 sites. In silico mutational analyses in monomer A showed that the single amino acid mutant, Thr101Ala (which mimics the de-phosphorylated state of NRT1.1), breaks the rigid cluster that is responsible for allosteric communication into two distinct clusters, whereas the mutant Thr101Asp (which mimics the phosphorylated state of NRT1.1) maintains the intact allosteric rigid cluster. This finding is in parallel with the experimental result of Ho et al. (2009). Therefore, these results suggest that the priming of the T101 site in monomer A for the phosphorylation is allosterically triggered by the high-affinity nitrate binding, whereas in monomer B, such allosteric communication and priming are absent (Rashid et al., 2018, 2019).

The NRT1.1 protein functions as a toggle shift via the phosphorylation/dephosphorylation of T101, a functional switch for regulating nitrate signalling and transport. Nitrate binding to NRT1.1 is responsible for generating special calcium waves through the action of phospholipase C, and blocking the induction of these waves could severely influence several nitrate-induced responses (Riveras et al., 2015; Armijo and Gutiérrez, 2017). For this phosphorylation, activities of the CBL9-CIPK23 complex towards NRT1.1 appear to be dependent on these calcium waves (Ho et al., 2009; Léran et al., 2015). More recently, the dimerization switch of NRT1.1 was confirmed to play an important role in creating cytoplasmic calcium waves sensed by CBL9, which activates the kinase, CIPK23, at low nitrate concentrations, which is inhibited at high nitrate concentrations (Rashid et al., 2018, 2019). Because dimerization itself can change the binding affinity of NRT1.1, the relative intermonomer dynamics were demonstrated to have strong connections with dimer coupling/decoupling. At low external nitrate concentrations, nitrate binds only to the high-affinity monomer A, which induces significant changes in collective atomic motions and causes the loss of interface area and priming dimer decoupling. The resulting conformational dynamics also reorient the nitrate-channelling helices, inhibiting nitrate binding at low-affinity monomer B. Altogether, binding of nitrate at the high-affinity monomer initiates NRT1.1 dimer decoupling and priming of the T101 site for phosphorylation activated by CIPK23 at low nitrate concentrations. This monomeric state of NRT1.1 acts as a high-affinity nitrate transceptor. However, when nitrate binds to both monomers, the dimeric state of NRT1.1 is maintained, with concurrent attenuation of CIPK23 activity, thereby regulating low-affinity nitrate signalling and transport (Figure 1).

NRT1.1 has been reported to contribute to the bulk of total nitrate uptake in roots via the mechanism of one nitrate ion and two protons symport across the plasmalemma (Huang et al., 1996; Wang et al., 2012). Recently, NRT1.1 was proposed to play an important role in plant tolerance to H⁺ toxicity. By examining the H⁺ tolerance of nrt1.1 knockout mutants, an uptake- and sensing-decoupled mutant, chl1-9 (which has reduced nitrate uptake but exhibits normal nitrate sensing activity; Ho et al., 2009), and wild-type plants, these nrt1.1 mutants were found to have reduced H⁺ tolerance compared with the wild type, indicating that nitrate uptake activity was required for the NRT1.1-conferred H⁺ tolerance. Further experiments in these plants also revealed that NRT1.1-conferred H⁺ tolerance of plants is closely related to the enhanced rhizosphere pH as a consequence of the increased nitrate absorption stimulated by H⁺ toxicity (Fang et al., 2016; Feng et al., 2020). In conclusion, H⁺ in the rhizosphere induces H⁺-coupled NO₃⁻ uptake by NRT1.1, thus altering the rhizosphere pH. Therefore, this function is largely attributable to the direct effect of NRT1.1 uptake activity. However, information on how plants perceive acid stress is still required in order to better understand the role of NRT1.1 in plant response to proton stress.

Drought and high salt are two major abiotic stresses that retard plant growth and reduce crop yield. Plants grown in nature have developed unique and overlapping resistance mechanisms in response to drought and salt stress (Zhu, 2016). Although NRT1.1 has been reported to participate in plant resistance to these two types of stress, their control mechanisms seem to have no intersection. Drought stress is well known to trigger the production of abscisic acid (ABA), which in turn leads to stomatal closure and induces the expression of several stress-related genes to acquire drought resistance in plants (Mittler and Blumwald, 2015; Jogawat et al., 2021). Nevertheless, NRT1.1-regulated plant resistance to drought might not be associated with ABA, as exogenous ABA application to leaves caused no significant difference in stomatal apertures between wild-type plants and nrt1.1 mutants (Guo et al., 2003). NRT1.1 is also expressed in Arabidopsis guard cells. The nrt1.1 mutants were found to have smaller stomatal apertures and thus more drought tolerance than wild-type plants grown in the medium with nitrate, which might be due to a lack of NRT1.1 and decreased nitrate accumulation in guard cells and failed to show nitrate-induced membrane depolarisation (Guo et al., 2003). This finding suggests that the inhibition of NRT1.1-mediated NO₃⁻ transport into guard cells may enhance plant resistance to drought stress, but the mechanisms underlying this are still elusive. Notably, it was reported recently that ABA signalling negatively regulates nitrate acquisition via phosphorylation of NRT1.1 by SnRK2s in Arabidopsis under nitrogen deficiency (Su et al., 2021). Several researchers have also found that CIPK23 is involved in ABA responses (Léran et al., 2015; Reyes and Grégory, 2020; Su et al., 2021). Therefore, endogenous ABA might play an important role in modulating NRT1.1-mediated NO₃⁻ transport during drought stress via two routes, including CIPK23 and SnRK2. Future work should concentrate on the molecular mechanisms connecting ABA to NRT1.1 under drought stress.

As the presence of nitrate enhances both root Na⁺ uptake and shoot Na⁺ accumulation in plants (Álvarez-Aragón et al., 2016), one or several nitrate transporters might modulate Na⁺ transport in plants. Although Na⁺ accumulation in the nrt1.1 mutants was significantly lower than that in wild-type plants, this difference was abolished when nitrate was removed (Álvarez-Aragón and Rodríguez-Navarro, 2017). This finding indicates that NRT1.1 either partly mediates or modulates NO₃⁻-dependent Na⁺ transport. However, a more recent study by Liu et al. (2020) proposed novel ideas of NRT1.1-conferred salt stress in plants. According to these researchers, several plant species fed NH₄⁺ were more hypersensitive to NaCl stress and acquired more Cl⁻ and less Na⁺ than those fed NO₃⁻. Further investigation of Arabidopsis showed that salt stress induced by the supply of NH₄⁺ was abolished by the removal of Cl⁻ but was not mitigated by Na⁺ removal, implying that excess Cl⁻ rather than Na⁺ is responsible for NH₄⁺-conferred salt hypersensitivity. Because NRT1.1 also participates in root Cl⁻ acquisition, NRT1.1 knockout in plants reduced their root Cl⁻ uptake and alleviated NH₄⁺-aggravated salt stress in plants. Therefore, the potential mechanisms of NRT1.1-conferred salt stress in plants might be closely related to the form of nitrogen supplied to the growth medium. In brief, NRT1.1 intensifies Na⁺ accumulation in plants grown with NO₃⁻ but entraps plants in a Cl⁻-excess status under NH₄⁺ conditions. How NRT1.1 balances NO₃⁻ and Cl⁻ uptake in response to salt stress under conditions of different NO₃⁻ and NH₄⁺ levels still needs to be explored.

Heavy metals affect plant growth and development and lead to severe human health hazards through contaminated food chains. NRT1.1 has been reported to be involved in regulating plant resistance to several heavy metal stresses (Mao et al., 2014; Jian et al., 2018; Zhu et al., 2019; Pan et al., 2020). Mao et al. (2014) found that the loss of NRT1.1 in plants under Cd treatment increased biomass and caused less uptake of Cd in both roots and shoots in the presence of nitrate, whereas no difference was observed between the nrt1.1 mutants and wild-type plants in the absence of nitrate. This finding indicates that the functional disruption of NRT1.1 reduces Cd uptake, which enhances Cd tolerance based on NO₃⁻ uptake activity. However, Jian et al. (2018) reported that wild-type plants are more Cd tolerant than the nrt1.1 mutants, as more Cd and nitrate are allocated to the vacuole of roots, which is correlated with transcript level repression of NRT1.5 but upregulation of NRT1.8. The distinct expression levels of NRT1.5 and NRT1.8 in the wild-type and nrt1.1 mutants also suggested that the expression of these two genes is regulated by NRT1.1 (Gojon and Gaymard, 2010). This discrepancy may be related to the variance of nitrate or iron concentrations in growth conditions between the two experiments, which are believed to markedly affect Cd uptake by roots in many studies (Yang et al., 2016; He et al., 2017; Zhu et al., 2020). Although the two studies provide different, even partly conflicting, results regarding the role of NRT1.1 in mediating Cd stress response in Arabidopsis, both processes require the coordination of NO₃⁻ transport.

Similarly, the indirect effect of NRT1.1 nitrate transport activity was found to play a role in plant resistance to Zn stress. The lack of NRT1.1 function in nrt1.1 mutants led to reduced accumulation of Zn in both roots and shoots under Zn stress, suggesting that the modification of NRT1.1 activity might also enhance the Zn tolerance of plants in an NO₃⁻ uptake-dependent manner (Pan et al., 2020). Notably, the mechanism by which NRT1.1 confers resistance to Pb stress in plants markedly differs from that of NRT1.1 in Cd and Zn stresses. Loss of NRT1.1 function in plants caused greater Pb toxicity and higher Pb accumulation in NO₃⁻-sufficient growth medium. The reduced Pb uptake in wild-type plants was further found to result from the reduction of Pb bioavailability in the rhizosphere due to H⁺ consumption during NO₃⁻ uptake by NRT1.1 (Zhu et al., 2019). In addition, exogenous application of low Mo in plants has been shown to induce the transcript levels of NRT1.1 (Liu et al., 2017). Collectively, these reports show that NRT1.1-associated strategies may be useful for manipulating the absorption and accumulation of heavy metals in plants; however, the chemical features of the heavy metals per se should be carefully considered. With respect to much of the progress concerning the molecular mechanisms of NRT1.1-regulated resistance to heavy metal stresses in Arabidopsis, the physiological relevance of these findings in crop species needs to be thoroughly studied.

Low potassium (K⁺) concentrations in most soils often limit plant growth (Maathuis, 2009). Although many potassium channels and transporters have been identified over the past few decades (Wang and Wu, 2017). the molecular mechanisms underlying potassium transport and regulation in plants require a more complete understanding. Recently, nitrate transporter 1.5 (NRT1.5), initially characterised as a pH-dependent bidirectional nitrate transporter, has been shown to be involved in K⁺ allocation in plants (Drechsler et al., 2015; Li et al., 2017). Fang et al. (2020) also found that the loss of NRT1.1 in nrt1.1 mutants disturbs K⁺ uptake and root-to-shoot allocation, resulting in greater growth arrest under low K⁺ stress conditions. Further physiological and genetic evidence revealed that both the uptake and root-to-shoot allocation of K⁺ in wild-type plants require the expression of NRT1.1 in the root epidermis-cortex and central vasculature. NRT1.1-involved coordination of NO₃⁻ and K⁺ uptake and allocation largely relied on the interactions between NRT1.1 and K⁺ channels/transporters located in the root epidermis-cortex and central vasculature. Given that the uptake rates of NO₃⁻ and K⁺ are often found to be positively correlated (Coskun et al., 2016), the activity of nitrate transporters in roots may be affected by K⁺, as evidenced by the observation that appropriate K⁺ supply clearly increased the expression of NRT1.1 in roots (Xu et al., 2020). Notably, Fang et al. (2020) revealed that these K⁺ uptake-related interactions are dependent on an H⁺-consuming mechanism associated with the H⁺/NO₃⁻ symport facilitated by NRT1.1. Nevertheless, NRT1.5-involved K⁺ loading into the xylem was verified to be only associated with its role as a proton-coupled H⁺/K⁺ antiporter (Li et al., 2017), which is not associated with NO₃⁻ transport. However, the detailed molecular mechanisms of such interactions in root K⁺ uptake, xylem K⁺ loading with NO₃⁻, and the involvement of NRT1.1 and K⁺ channels/transporters in this process are still unclear.

Ammonium (NH₄⁺) can be utilised as a predominant nitrogen source in some plant ecosystems, but becomes toxic at high concentrations, especially when available as the sole nitrogen source (Gao et al., 2010; Ruan et al., 2016). The presence of an appropriate concentration of nitrate can clearly alleviate NH₄⁺ toxicity in many plant species (Roosta and Schjoerring, 2007; Hachiya et al., 2011). However, NRT1.1-mediated nitrate uptake did not appear to play a positive role in plant tolerance to NH₄⁺ toxicity, as the functional disruption of NRT1.1 in plants caused higher tolerance to high NH₄⁺, and the application of nitrate did not enhance the ammonium tolerance of nrt1.1 mutants (Hachiya and Noguchi, 2011). Therefore, a nitrate-independent function of NRT1.1 could exist. Jian et al. (2018) proposed that high NH₄⁺ levels induced the activities of NADH-dependent glutamate dehydrogenase and glutamic-oxaloacetic transaminase in NRT1.1 knockout mutants chl1-1 and chl1-5, which reduced NH₄⁺ accumulation and thus improved tolerance to NH₄⁺ toxicity. Because the NRT1.1 P492L point mutant chl1-9 retains normal function in nitrate signalling, the similar sensitivity symptoms of chl1-9 and the wild type in response to high NH₄⁺ indicate that the existence of the signalling function of NRT1.1 is sufficient to induce NH₄⁺ toxicity. Given that the phosphorylation state and NRT1.1 protein levels in chl1-9 are similar to those of the wild type, the decreased assimilation rate of NH₄⁺ in wild-type plants could also occur in chl1-9 mutants, which results in NH₄⁺ toxicity (Hachiya and Noguchi, 2011; Jian et al., 2018). However, convincing experimental data are still needed. Another plausible interpretation of the different tolerance to NH₄⁺ toxicity in NRT1.1 knockout mutants chl1-1 and chl1-5 and NRT1.1 P492L point mutant chl1-9 is that they may show different capacities for NH₄⁺ uptake. The existence of NRT1.1 plays a positive role in inducing the expression of AMT1s and NH₄⁺ uptake (Jian et al., 2018). Although whether this mechanism is indeed involved in chl1-9 needs to be further confirmed by biological analyses, it is worth assuming that the NRT1.1 in chl1-9 is likely involved in NH₄⁺ uptake. As a common component, CIPK23 was previously shown to directly interact with and phosphorylate the ammonium transporters AMT1; 1/2 and nitrate transporter NRT1.1, modulating their activity (Ho et al., 2009; Straub et al., 2017; Tian et al., 2021). It has been shown that the CBL9-CIPK23 complex is inhibited by NRT1.1 dimer (Rashid et al., 2018), which implies that the altered phosphorylation state of NRT1.1 in chl1-9 could affect the activity of AMT1 proteins under control of different nitrogen signals (Wu et al., 2019). Accordingly, the signalling function of NRT1.1 might play a positive role in mediating NH₄⁺ uptake and accumulation. In addition, NRT1.1-related NH₄⁺ toxicity has been shown to be associated with ethylene and auxin synthesis (Esteban et al., 2016; Jian et al., 2018). However, more studies are needed to elucidate how ethylene and auxin are involved in modulating the ammonium tolerance of nrt1.1 mutants.

Nutrient deficiency can seriously deter the normal growth of plants and consequently result in a reduction in crop yield (Shrestha et al., 2020). The mechanisms regulating plant responses to single nutrient stress have been documented over the past few decades (Wang and Wu, 2013; Tewari et al., 2021). However, much remains to be studied, especially if one specific component is selected as a molecular technique to improve the resistance of plants to different nutrient deficiency stresses. Interestingly, NRT1.1 has been shown to be involved not only in regulating the resistance of Arabidopsis to low-K⁺ stress, but also in responding to P and Fe nutrient deficiencies. In a study by Medici et al. (2015), an early nitrate-inducible transcription factor (TF), HRS1 and its close homologue HHO1, was reported to repress primary root growth caused by P deficiency, but only when nitrate is present, suggesting a complex regulation of N and P signals. In another recent study, Medici et al. (2019) found that the phosphate starvation response (PSR) can be actively controlled by N supply, and this process also relies on a combination of local and long-distance systemic nitrate signalling pathways. PHOSPHATE2 (PHO2) transcript accumulation is upregulated by nitrate depletion, which is dependent on NRT1.1. However, most PSR genes were not found to be regulated by nitrate in the PHO2 mutants, indicating that PHO2 integrates nitrate signals into the PSR. Furthermore, NRT1.1 was repressed by P starvation and PHO2 acted as a positive regulator of NRT1.1, as the transcript levels of NRT1.1 in the PHO2 mutant were lower than those in the wild type (Huang et al., 2013; Medici et al., 2015, 2019). These results provide important insights into the underlying molecular mechanism by which N and P signalling pathways interact.

Recently, several studies have demonstrated that the dependence of PSR on nitrate availability is conserved across a wide range of plant species (Hu et al., 2019; Medici et al., 2019; Wang et al., 2020a). In rice, high nitrate supply increased P acquisition and induced the transcript levels of P transporter (PT) genes and P starvation-induced (PSI) genes, which correlates with an increase biomass of rice. However, this nitrate induction of PSI genes was found to be abolished in mutants of the OsNRT1.1B transporter, the orthologue of AtNRT1.1 in rice, indicating that the nitrate-triggered P response is dependent on OsNRT1.1B function (Hu et al., 2019). Hu et al. further found that nitrate-stimulated interaction of OsNRT1.1B with OsSPX4 facilitates the ubiquitination and degradation of the P signalling repressor protein OsSPX4, which allows the release of OsPHR2 (Zhou et al., 2008), a master TF of phosphate signalling, into the nucleus and activates the transcription of P utilization genes. Importantly, OsSPX4 was also shown to interact with and control the activity of the master TF of nitrate signalling, OsNLP3, in rice. Therefore, nitrate-stimulated degradation of OsSPX4 activates expression of phosphate and nitrate uptake genes, ensuring a coordinated utilization of N and P in plants (Hu et al., 2019; Poza-Carrión and Paz-Ares, 2019). In addition, a nitrate-inducible, GARP-type transcription repressor 1.2 (NIGT1.2) was found to modulate P and nitrate uptake in response to P starvation in Arabidopsis. Under P deficiency conditions, NIGT1.2 directly upregulated the expression of the phosphate transporter genes PHT1;1 and PHT1;4 and downregulated transcription of NRT1.1 via binding to cis-elements in their promoters. The authors also identified a similar regulatory pathway in maize (Wang et al., 2020a). Collectively, these findings highlight the complexity of the nitrate and phosphate responses, with NRT1.1 having a crucial conserved role in modulating the interaction. Further studies are needed to investigate the relevant downstream signal transduction pathways of this N–P integrator.

Liu et al. (2015) reported that the lack of NRT1.1 enhances plant tolerance to Fe deficiency stress; however, the expression of Fe acquisition related-genes FRO2, IRT1, and FIT was lower in the nrt1.1 mutants than in wild-type plants under Fe-deficient conditions, indicating that the FIT-dependent Fe deficiency signalling pathway was not involved in NRT1.1-regulated Fe deficiency responses. Because nitrate functions as a nutrient and a signalling molecule (Krouk, 2017), it is conceivable that the reduced accumulation of internal nitrate in nrt1.1 mutants may impair the FIT-dependent Fe deficiency signalling pathway. However, more detailed studies are needed to explore the mechanisms underlying the NRT1.1-regulated Fe deficiency responses. Overall, a clear link was found between NO₃⁻ and P, K, or Fe in the transport and signalling cascade (of NO₃⁻) coordinated via NRT1.1 in plants. However, an in-depth understanding of the effects of the crosstalk between nitrogen and one or more nutrients is still necessary, which is very important for understanding and engineering plant adaptive responses to a fluctuating nutritional environment.