Researchers at Michigan State University have discovered two proteins that work together to determine the fate of cells in plants that encounter certain stresses.
Ironically, an important discovery in this finding, recently published in Nature communicationwas made up for when the project leader prepared to de-stress.
Postdoctoral researcher Noelia Pastor-Cantizano was taking a bus to the airport to go on vacation when she decided to share a promising result she had helped collect a day earlier.
“I didn’t want to wait 10 days until I got back to send it in. It took almost two years to get there,” says Pastor-Cantizano, who was then working in the Brandizzi lab in the MSU-DOE Plant Research Laboratory, or PRL.
“That’s what I remember right now,” Pastor-Cantizano said. “I thought, ‘I can relax now, at least for a week.’
Pastor-Cantizano was identifying a gene in the model plant Arabidopsis that could control the plant’s response to stressors, which could lead to the plant’s death. She and her collaborators had identified a protein in Arabidopsis that seemed to determine whether a plant would live or die under stress conditions.
Identifying the gene was just the beginning of the story, even though we had been on the road for years. It would take another five years to arrive at this new article.
The researchers found that the proteins BON-associated protein2, or BAP2, and the inositol-requiring enzyme 1, or IRE1, work together to cope with stress conditions – a matter of life or death for plant cells.
By understanding how these proteins function, researchers can breed plants that are more resistant to dieback.
Creating plants that are more resistant to endoplasmic reticulum stress, or ER stress, has widespread implications for agriculture. If crops can be made more resilient in the face of drought or heat, the plants have a better chance of surviving and thriving despite the changing climate.
“Research in our laboratory is fueled by enthusiasm and gratitude to make important contributions to science,” said Federica Brandizzi, MSU Research Foundation Professor in the Department of Plant Biology and at PRL. “The work was enormous and was only possible thanks to the patience, enthusiasm and dedication of a great team. Noelia was simply fantastic.”
To collaborate
Within eukaryotic cells is an organelle known as the endoplasmic reticulum or ER. It creates proteins and folds them into shapes that the cell can use. Just like cutting vegetables to use in a recipe, the proteins must be formed into the correct shape before they can be used.
The protein making and protein folding capabilities must be balanced, like a sous chef and a chef working together. If the sous chef provides the chef with too few or too many ingredients, the balance in the kitchen is disrupted.
When the ER cannot do its job properly, or the balance is disrupted, it enters a state known as ER stress. The cell will trigger a mechanism known as the unfolded protein response, or UPR, to decide what to do next. If the problem can be resolved, the cell will take life-saving measures to resolve the problem. If this is not the case, the cell begins to shut down, ending the life of the cell and possibly the life of the plant.
It was known that the enzyme IRE1 was responsible for controlling the mechanisms that would save or kill the cell.
But what calls IRE1 to action?
In this study, researchers from the Brandizzi laboratory were looking for the master regulator of these pro-death processes, known as programmed cell death.
“I came up with the idea because I read that irritable bowel disease is linked to a mutation in a gene controlled by IRE1 that occurs in humans,” Brandizzi said. “People are diverse and so are plants. That’s why I thought to explore plant diversity as a source of new important findings in the UPR.”
The researchers started by looking at hundreds of accessions, or plants of the same species, but specific to one location. For example, a plant growing in Colombia will have genetic variations from the same plant species growing in Spain, and the way they respond to stress conditions may differ.
They found extensive variation in the response to ER stress between the different accessions. By taking the accessions whose responses were the most different, they tried to identify the differences in their genomes. This is where the BAP2 gene candidate came into play.
“We found that BAP2 responds to ER stress,” says Pastor-Cantizano, currently a postdoc at the University of Valencia. “And the nice thing is that it can control and modify the activity of IRE1. But IRE1 can also regulate BAP2 expression.”
BAP2 and IRE1 work together and signal to each other what is the best course of action for the cell. Having one without the other results in plant death when ER homeostasis is out of balance.
Seven years
From start to finish, this project took more than seven years of dedicated work.
Day in and out, the researchers spent their time placing seeds on plates with a medium in which to grow. Arabidopsis seeds, at their smallest, are not much bigger than grains of sand, so this was delicate work that required time and attention.
From there, the researchers spent several more months with these plants, looking at the accession’s offspring and identifying how BAP2 worked in the plants. This continued for a few more years.
“It has been a long road with its obstacles, but it has been worth it,” Pastor-Cantizano said. “When I started this project, I couldn’t imagine how it would end.”
This work was funded by the National Institutes of Health, with contributory support from the Division of Chemical Sciences, Geoscience and Biosciences, Office of Basic Energy Sciences, Office of Science, US Department of Energy; the Great Lakes Bioenergy Research Center, U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research; and MSU AgBioResearch. Additional contributory support comes from the Generalitat Valenciana, “European Union NextGenerationEU/PRTR.”
