To ensure stable yields, crops must adapt to many concurrent fluctuating stresses, such as low temperatures and limited availability of the nutrient phosphorus, which is present in the soil as inorganic phosphate (P i ). Both low temperature and limited P i cause notable yield loss, a challenge that is aggravated by the fact that cold stress directly inhibits P i uptake 1 .

Writing in Nature, Liao et al. 2 reveal the molecular mechanisms by which the protein NLA coordinates enhanced cold tolerance and reduced P i uptake. Furthermore, the authors successfully decouple cold tolerance and P i uptake by rationally engineering the NLA protein, resulting in high-yield varieties of maize (Zea mays, also known as corn) that have superior performance under cold stress and improved phosphorus-use efficiency compared with varieties with non-engineered NLA.

Phosphorus is an essential nutrient that plants absorb as P i . A group of proteins containing a domain called SPX are intracellular sensors of P i levels 3 , 4 . Focusing on the SPX family in maize, the authors used the gene-editing system CRISPR–Cas9 to make two versions of non-functioning NLA. Compared with non-edited plants, plants with the edited NLA had increased sensitivity to cold and higher levels of P i uptake. Previous studies have mainly focused on the role of SPX proteins in P i sensing 5 , and their function in response to cold has been unclear. Liao and colleagues reveal that NLA responds to low temperature at both the gene-expression level and the level of protein that the gene encodes to confer cold tolerance. The authors ultimately establish a previously unknown mechanism for SPX family proteins in cold adaptation.

SPX proteins are divided into four groups known as clades. NLA belongs to the SPX-RING clade that can also add the protein ubiquitin to target proteins, thereby marking them for degradation. The authors searched for target proteins that NLA could bind and add ubiquitin to. Liao and colleagues thereby selected the proteins JAZ11, which has a role as a repressor of the signalling pathway mediated by the hormone jasmonic acid (which helps plants to withstand cold conditions 6 , 7 ) and PT4 (which has a role as a P i transporter 8 ) for further investigation.

The authors demonstrated that NLA physically interacts with and adds ubiquitin to JAZ11 and PT4 to promote their degradation, and this results in enhanced cold tolerance and decreased P i uptake (Fig. 1a). Genetic manipulation that increased or eliminated expression of the JAZ11 and PT4 genes that encode NLA targets altered cold sensitivity and phosphorus levels, respectively, confirming the role of NLA. Crucially, an analysis of diverse inbred varieties of maize revealed natural examples of variations in the sequences of JAZ11 and PT4 related to sequences corresponding to amino acids at which the encoded protein can attach to ubiquitin. These variations promote either JAZ11 degradation or decrease PT4 degradation.

The physical interaction between NLA and PT4 is dependent on the level of molecules called inositol polyphosphates (InsP), whereas the interaction between NLA and JAZ11 is not. This InsP-dependent specificity provides a possible avenue to increase cold tolerance without the penalty of reduced P i uptake.

Guided by structural predictions of the binding of the NLA and InsP complex, the authors identified a specific region of NLA that might be key to InsP binding and then investigated the effect of engineering mutations that correspond to this region of interest. One mutant variety of plants that Liao and colleagues generated, which had four amino acids removed from NLA, had enhanced cold tolerance and increased P i uptake compared with plants that retained these amino acids (Fig. 1b). Subsequent tests confirmed that this alteration reduced InsP binding to NLA by 50-fold and resulted in a highly reduced interaction between PT4 and NLA, but JAZ11 binding to NLA was unaffected.

This work highlights the key function of NLA in integrating the jasmonic acid signalling pathway with the pathway that mediates P i transport. Two regulatory layers are at work — the expression of NLA is induced by cold stress, and NLA is stabilized at low temperatures.

However, the exact mechanism by which maize plants sense cold and thereby fine-tune NLA activity remains unclear. Direct cold sensing by NLA seems unlikely, given that the changes in transcription of NLA in response to the cold take at least 12 hours to happen. A calcium signalling pathway is reported 9 − 11 to have key roles in sensing cold stress and transmitting signals that alter the expression levels of cold-responsive genes. Whether NLA is a target of this calcium-mediated cascade requires further study. Identifying the factors that regulate NLA might aid precise optimization of its activity, enabling an ideal balance between cold tolerance and phosphate uptake.

A key question emerges from the authors’ findings. Can this type of two-in-one strategy be extended to boost the uptake of other nutrients, such as nitrogen? This is relevant because soil nitrogen availability is strongly influenced by mean annual temperature 12 , and a well-established interplay exists between regulatory proteins that function in both nitrogen and phosphorus signalling pathways 5 . In the model plant Arabidopsis thaliana, loss of NLA disrupts its ability to adapt to limited availability of nitrogen 13 . Gaining a better understanding of NLA’s functions and exploring its role in coordinating responses to other stresses and in other crop species would be of great interest.

The jasmonic acid signalling pathway helps plants to deal with many types of stress. As well as targeting and degrading JAZ11, the authors found that NLA targets genes encoding proteins that are responsive to other plant hormones, such as auxin and abscisic acid. Together, these observations suggest that there is a comprehensive network that mediates resilience to cold conditions, with NLA acting as a central hub that moderates crosstalk between multiple hormone signalling pathways. Investigating this network might reveal new targets for breeding high-yielding crops that cope well with cold conditions.

The role of NLA in stabilizing crop yield was confirmed under both controlled greenhouse conditions and in comparatively more varied outdoor field conditions. In the authors’ experiments, cold exposure was maintained at 4 °C, whereas the field trials experienced temperature fluctuations throughout the day and night. This highlights the need to characterize NLA’s response to daily rhythms under field conditions. This is a prerequisite for adjusting its activity in ways that would be effective for crops grown in the field that would have to adjust to temperature changes.

The authors’ work provides a notable example of how to examine the molecular mechanisms underlying the trade-offs between responses to stress and boosting yield. The research moves beyond just investigating stress responses in isolation, and points the way to understanding integrated responses, demonstrating how a single protein, such as NLA, can coordinate multiple pathways to balance the needs of plant survival with plant productivity. This integrative approach will be crucial for breeding crops that are suited to the complex, fluctuating stresses of future climates.