ENERGY BALANCE

Master Signals Govern Plant Response to Range of Stresses

Kinases Correspond to Mammalian Energy Sensor AMPK

When things get rough for plants, they can’t simply move to a new environment with better conditions. They have to adapt their own metabolism to face the challenge, whether it is dryness or cold or a chemical insult. And since plants feed on light, every night is a period of starvation; the constructive activities of the cells cease, and the plant begins to break down its own parts to fuel itself.

Graham Ramsay

Jen Sheen (right) and Elena Baena-Gonzalez found that when plants get stressed, two protein kinases activate a broad survival response.

Common Signal
As a species that depends on plants for food, people have an interest in helping our green friends buffer themselves against stress. Researchers have actively studied the stress response, uncovering genes that respond to different kinds of challenge, including darkness, drought, cold, lack of oxygen, and herbicides. But new findings from the lab of Jen Sheen, HMS professor of genetics at Massachusetts General Hospital, suggest that these diverse insults do not trigger merely unique responses in a plant’s cells; instead, they are integrated into a general signal of the plant’s status. In the Aug. 23 Nature, her team details two protein kinases that are responsible for switching on a wide program of genetic change in response to many different stresses, the same class of kinase responsible for energy regulation in human cells.

Genomic studies on plants have produced large sets of data about their responses to different conditions. But when research fellow Elena Baena-Gonzalez began looking at the data, she noticed something interesting. A set of genes classified as dark-induced genes, which had been shown to become active in response to darkness, were also activated by other stressors. The finding “told us that this is not really specific—there must be some common signal of different types of stress,” she said. Another clue came from data on plants that were given extra nutrition in the form of sugar. This treatment repressed dark-induced genes, even when the plant was in darkness. “The sugar addition overrode the dark–light signal,” Baena-Gonzalez explained.

To investigate the connection further, the team began looking at perturbations in the plant Arabidopsis that activated the dark-induced gene DIN6. They found that a protein kinase inhibitor blocked the gene’s activation, and they went on to test a family of protein kinases that had been shown to be crucial metabolic regulators in yeast and mammals. Two of these proteins, KIN10 and KIN11, switched on dark-induced genes when they were expressed in the leaves of Arabidopsis.

The team then examined the effect of KIN10 on early gene expression and uncovered a whopping 1,000 or more potential target genes whose expression was altered by the protein kinase activity. Sheen noted that such a broad effect on gene expression is unusual. “This has to be a master regulator,” she said. This set of target genes overlapped with gene expression profiles of plants under various stress conditions. KIN10 turned on genes involved in catabolism—the degradation of components of the plant cell as extra sources of fuel—while it shut off genes involved in anabolism, energy-taxing construction projects in the cell. The protein kinase also controlled more than a hundred transcription factors, suggesting it had even further effects on cell function through downstream cascades of gene transcription.

The team then overexpressed KIN10 in plants or removed it through gene silencing. They found that when the kinase was overexpressed and a plant was given plenty of light and nutrients, it developed more slowly but lived longer. This meager growth persisted even when the plants were provided continuous light and sugar. “It’s like they are in a permanent state of starvation,” Baena-Gonzalez said. When deprived of nutrients, however, a condition that sent normal plants into senescence, the KIN10-overexpressing plants survived. When KIN10 and KIN11 were both silenced to eliminate their redundant functions, plants failed to develop properly and died early, suggesting that the two are important for normal development as well as more immediate responses to the environment.

Energy Indicator
Sheen said that plants do have specific ways of sensing different stresses. But somehow, the stress signals generated by those conditions all converge into something very general. The ultimate effect on the plant is not dependent on light, or darkness, or even sugar. “It’s actually the energy status of the plant” that serves as the barometer for its responses, Sheen said.

A state of starvation. Plants with KIN10 overexpression (center, right) develop much more slowly than normal plants (left), even when given extra light and nutrients.

A similar process takes place in mammalian cells, governed by AMPK, which is a functional homologue to KIN10 and KIN11. AMPK acts as an energy sensor that helps to maintain the energy balance in the cell. It is activated when the cell’s level of AMP rises and the level of ATP—the energy currency of the cell—drops as energy is depleted. Sheen said that similar expression studies are trickier to do with AMPK, but she guesses they may have similar wide-reaching effects on gene expression in the mammalian cell. Sheen noted that KIN10 overexpression triggered effects similar to caloric restriction in other organisms. AMPK is a target of the diabetes drug metformin and the red wine derivative resveratrol, and is also activated by exercise and by natural signals of energy balance such as leptin.

Grahame Hardie, professor of cell signaling at the University of Dundee, said that while this family of related molecules has been well characterized in mammals and in fungi, this paper “is now beginning to give a good understanding of its role in plants.” Research increasingly shows that AMPK and its related protein kinases in other organisms perform the same functions, he said, even though the stresses that each organism faces are very different. It may be that these protein kinases control an ancient starvation response in eukaryotic cells.

—Courtney Humphries

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