Researchers at Michigan State University (MSU) have recently identified two proteins that collaborate to determine the fate of cells in plants under stress. This significant finding, recently published in Nature Communications, was ironically made just as the project’s leader was preparing to unwind.
Postdoctoral researcher Noelia Pastor-Cantizano was en route to the airport for a vacation when she decided to share a promising result she had gathered the previous day.
“I didn’t want to wait ten days until I came back to send it. It took almost two years to get there,” said Pastor-Cantizano, who was then part of the Brandizzi lab at the MSU-DOE Plant Research Laboratory (PRL). “I was thinking ‘I can relax now, at least for one week,’” she added.
Pastor-Cantizano had been working to identify a gene in the model plant Arabidopsis that could control the plant’s response to stressors, which can lead to its death. She and her team had pinpointed a protein in Arabidopsis that seemed to dictate whether a plant would survive or perish under stress conditions.
However, identifying the gene was just the beginning, despite already being years into the project. It took an additional five years to reach the conclusions presented in the new paper.
The research revealed that the proteins BON-associated protein2 (BAP2) and inositol-requiring enzyme 1 (IRE1) cooperate under stress conditions – a critical issue for plant cells. Understanding how these proteins function together can help scientists develop plants that are more resilient to adverse conditions.
Creating plants that are resistant to endoplasmic reticulum (ER) stress has significant implications for agriculture. If crops can be bred to withstand drought or heat better, they stand a better chance of thriving despite the changing climate.
“Research in our lab is fueled by enthusiasm and gratitude to be able to make important contributions to science,” said Federica Brandizzi, MSU Research Foundation Professor in the Department of Plant Biology and at the PRL.
“The work was herculean and has been possible only thanks to the patience, enthusiasm, and dedication of a wonderful team. Noelia was simply fantastic.”
Within eukaryotic cells is an organelle known as the endoplasmic reticulum (ER), which creates proteins and folds them into shapes the cell can use. This process is similar to cutting up vegetables for a recipe – the proteins must be correctly shaped before they can be used.
Protein production and folding must be balanced, akin to a sous chef and a chef working together. When this balance is disrupted, the ER experiences stress, triggering a mechanism known as the unfolded protein response (UPR). The UPR decides whether to save or shut down the cell, potentially leading to the plant’s death.
It was known that the enzyme IRE1 directs mechanisms to either save or kill the cell, but what activates IRE1 remained unclear. The Brandizzi lab researchers were searching for the master regulator of these pro-death processes, known as programmed cell death.
“I had the idea because I read that irritable bowel disease is linked to a mutation in a gene controlled by IRE1 that occurs among humans,” Brandizzi said. “Humans are diverse, and so are plants. So I thought to look into plant diversity as a source of new important findings in the UPR.”
The researchers began by examining hundreds of accessions – plants of the same species but from different locales. For example, a plant from Colombia will have genetic variations compared to the same species in Spain, which may affect their stress responses differently.
The experts discovered extensive variation in the response to ER stress between different accessions. By examining the most dissimilar responses, they identified differences in their genomes, leading to the discovery of the BAP2 gene candidate.
“We found that BAP2 responds to ER stress,” said Pastor-Cantizano, now a postdoc at the University of Valencia. “And the cool thing is that it is able to control and modify the activity of IRE1. But also IRE1 is able to regulate BAP2 expression.”
BAP2 and IRE1 work together, signaling each other on the best course of action for the cell. Without both proteins, the plant dies when ER homeostasis is disrupted.
The project spanned over seven years of dedicated work, involving meticulous tasks like placing tiny Arabidopsis seeds onto growth plates and studying the plants’ offspring to understand how BAP2 functions.
“It has been a long road with its obstacles, but it has been worth it,” said Pastor-Cantizano. “When I started this project, I couldn’t imagine how it would end.”
This study highlights the collaborative work required to uncover the intricate mechanisms that enable plants to withstand stress, paving the way for future agricultural advancements.
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