When injured, plants trigger regenerative and defense processes. Until now, it has been unclear whether these “fix and fight” responses activate together or represent biological trade-offs.

A new study shows glutamate like receptor proteins (GLRs), known to mediate defense responses, can be blocked in cells near the site of injury, to initiate regenerative responses in wounded plants through changes in chromatin and transcriptional reprogramming. The study shows GLR mediated signals dial down the regeneration system and turn up the defense response.

Plant glutamate receptors mediate a trade-off between defense and regeneration, favoring defense. [Hernandez Coronado et al, Developmental Cell, 2022]
“In this investigation, we looked at chromatin changes during the hours after wounding, which led us to glutamate receptors. We expected them to be positive regulators of regeneration, but they turned out to be negative ones. This shows how even highly regenerative organisms such as plants, don’t necessarily devote all their resources into regeneration in their wound response,” said Kenneth Birnbaum, PhD, professor at New York University’s Center for Genomics and Systems Biology and the study’s senior author. “The good news is that there is room for improvement.”

Birnbaum’s team showed genetic and pharmacological inhibition of GLR activity increases regeneration efficiency in multiple organ repair systems in Arabidopsis (thale cress) and corn. Toward mechanistic insights, the authors showed GLRs act through salicylic acid signaling to down-regulate regeneration. Plants with mutations in the salicylic acid receptor are hyper-regenerative and partially resistant to manipulations of GLR activity.

These findings, reported in the journal Developmental Cell (“Plant glutamate receptors mediate a bet-hedging strategy between regeneration and defense”), uncover a mechanism that regulates the balance between defense and regeneration and has been conserved during evolution. For agricultural biotechnology and conservation efforts, the new study could offer strategies to improve plant regeneration in the face of attacks by microbes, insects, larger pests, and adverse changes in climate.

“Retuning the balance between plant defense and regeneration could be used to improve regeneration for biotechnology, conservation, and propagation of staple food crops,” said Birnbaum. “Breeding crops that more readily regenerate and can adapt to new environments is critical in the face of climate change and food insecurity.”

Images show the effect of a glutamate receptor antagonist on the plant’s “decision” to invoke defense response vs. regenerative processes (i.e., fight or fix). At left, a cut leaf shows a typical regenerative response, ultimately showing some regeneration. However, treatment with glutamate receptor antagonist, CNQX, forces the plant to augment regeneration and downregulate defense, as evident by increased root formation from leaves, a natural plant regenerative response. [Kenneth Birnbaum, PhD]
The researchers cut off tips of the plants’ roots in Arabidopsis and corn model systems, and found the plants initiate both regenerative and defense mechanisms but not to maximum capacity. They also found lowering one response increases the other.

Marcela Hernández Coronado, PhD, first author of the paper and a former postdoctoral researcher at NYU said, “The ‘fight or fix’ responses seem to be connected like a seesaw or scales—if one goes up, the other goes down. Plants are essentially hedging their bets after an attack.”

Since GLRs control both regeneration and defense responses, they can be targeted to improve crop growth, particularly cereal crops like corn, sorghum, and wheat that are resistant to regeneration.

“These glutamate receptors provide a ‘druggable target’ that we can use to enhance plant regeneration and propagation,” said Birnbaum.

The researchers blocked GLRs via genetics and drugs. José Feijó, PhD, led the genetic targeting study at his lab at the University of Maryland. His team generated “quadruple mutant” plants with mutations in four genes involved in GLR activity and found that the mutants were better at regeneration, which suggests that the mutations compromise the defense response. The researchers also used neuronal antagonists to inhibit GLR activity. These too tipped the plants’ decision-making process to favor regeneration.

Birnbaum said, “Having druggable targets for regeneration could have wide application for screening new crop germplasm and developing more efficient pipelines for regenerating transformed material. That could affect the throughput and the speed of new crop development, which will become increasingly important in the climate extremes that are soon expected, unfortunately.”

In future studies, Birnbaum’s team will delve further into the complexities of plants’ response to injury.

“We may not yet be done with tweaks that could downregulate defense in favor of regeneration. There may be other hormonal pathways that we can manipulate that could further improve regeneration,” said Birnbaum.