Updating the Textbook

According to Karl Popper, a theory or hypothesis can never be definitely proven, but it can be falsified. This implies that it should be rigorously tested for its validity. Scientific progress often involves revisiting and revising established textbook knowledge. A recent study at the Institute of Science and Technology Austria (ISTA) illustrates that once again, as it revises our understanding of the classical signaling pathway for the plant hormone auxin.

Plant cells are powerful machines. They convert external signals into internal actions that facilitate growth or energy conversion. For those processes to occur, a finely tuned signaling cascade transforms an external stimulus into a response.

The canonical signaling mechanisms for auxin, which acts as the major coordinative signal in plants, have been well established for decades. Now, a new study in Nature by the Friml group at the Institute of Science and Technology Austria (ISTA) revises this understanding, suggesting that auxin signaling in plants involves the second messenger cAMP—a key molecule that is notoriously known from animal cells.

A green thumb

“Tap-tap-tap” the ping pong ball bounces back and forth. “Whack!” It sails past Huihuang Chen’s racket into the corner. The game is over: Jiři Friml just won a tight match. “I should work on my ping-pong skills”, Chen laughs. Both scientists are in tense anticipation to see if their newest research results will be accepted by the journal. It is nerve-wracking for both scientists, and ping-pong serves as a welcome distraction.

While his racket swing needs some fine-tuning, Chen’s enthusiasm for plants and science does not need any improvement. What began rather unexpectedly in university soon became a passion, leading him to appreciate the macroscopic beauty and microscopic intricacies of plants. Now, the PhD student’s apartment is full of them—from succulents to various orchids. In the lab, his primary focus, however, is the mouse-ear cress, known as Arabidopsis thaliana (A. thaliana).

Auxin – a key hormone for plants

In 1880, Charles Darwin proposed the existence of auxin as a key plant hormone regulating growth. It drives phototropism (light-directed growth) and gravitropism (the process by which plants sense and respond to gravity), promotes cell elongation, and shapes the overall plant architecture. It also influences embryo and root development and fruit formation, and is widely applied in agriculture for propagation and yield enhancement.

Inside cells, auxin binds to the TIR1/AFB auxin receptors. This interaction triggers the degradation of Aux/IAA—repressors that block protein activities. Their removal leads to activation of ARFs (Auxin Response Factors). These proteins—transcription factors—subsequently switch on hundreds of genes, thus reprogramming cells in response to auxin. These signaling components have been extensively studied, providing us with a textbook example of a canonical signaling pathway. Now this understanding is being revised.

cAMP: The signal amplifier

“Our new study builds upon groundbreaking work by our former colleague, Linlin Qi,” says Chen. Qi, a former postdoc in the Friml group at ISTA, discovered that the auxin receptors possess adenylate cyclase activity, meaning they can produce cAMP (cyclic Adenosine Monophosphate)—a second messenger, well characterized in humans, which can amplify the original external signal. 

“This finding was completely unexpected and had the potential to revolutionize our understanding of plant hormone signaling and prompted us to investigate further: What role does cAMP play in auxin signaling?” Chen continues.

The scientists took Qi’s findings as a starting point and delved deeper into the function of cAMP in the auxin signaling pathway. Using a combination of genetic, biochemical, and physiological approaches, they systematically tested whether cAMP acts as a true second messenger in plants. In doing so, they explored how cAMP levels change in response to auxin and how these changes influence signaling events.

The results of the in-depth examination show that cAMP is indeed a critical second messenger in plants. “Sufficient levels of cAMP can bypass the need for auxin perception by the receptor, directly activating the auxin signaling pathway. This establishes cAMP as a bona fide second messenger in plants, a role that was previously well-documented in animals but highly debated in plants,” summarizes Friml the study.

In non-scientific terms, cAMP’s role is similar to a rock band amplifying their music (the signal) through microphones (the receptor) and projecting it via the sound system (the second messenger) to reach every corner of the music hall.

Opening new chapters

This new discovery is not intended to negate the existing model of auxin signaling; instead, it seeks to enhance and revise the current notion, by adding a new dimension. The drive to question and challenge existing knowledge and develop it further is the heart of basic research and an essential mission of ISTA.

Applied areas, like agriculture, could benefit from these new findings. By manipulating cAMP levels, one could fine-tune plant growth and stress responses, leading to improved crop yields and resilience. The same is true for biotechnological tools, where understanding how cAMP works in plants could help design synthetic signaling pathways for designing plants with desired traits.

With newfound determination, Chen picks up the table tennis racket and challenges Jiři Friml for another match. Perhaps this time around he comes up with a victory.

Publication:

H. Chen, L. Qi, M. Zou, M. Lu, M. Kwiatkowski, Y. Pei, K. Jaworski and J. Friml. 2025. TIR1 produced cAMP as a second messenger in transcriptional auxin signaling. Nature. DOI: 10.1038/s41586-025-08669-w

Funding information:

The ISTA part of this project was supported by funding from the European Research Council (ERC; 101142681 CYNIPS) and the Austrian Science Fund (P 37051-B).