Cellulose biosynthesis inhibitor isoxaben causes nutrient-dependent and tissue-specific Arabidopsis phenotypes

Authors: OGDEN, MICHAEL - University Of Copenhagen; Whitcomb, Sarah; KHAN, GHAZANFAR - La Trobe University; ROESSNER, UTE - Australian National University; HOEFGEN, RAINER - Max Planck Institute Of Molecular Plant Physiology; PERSSON, STAFFAN - University Of Copenhagen

Submitted to: Plant Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/24/2023
Publication Date: 10/12/2023
Citation: Ogden, M., Whitcomb, S.J., Khan, G.A., Roessner, U., Hoefgen, R., Persson, S. 2023. Cellulose biosynthesis inhibitor isoxaben causes nutrient-dependent and tissue-specific Arabidopsis phenotypes. Plant Physiology. kiad538. https://doi.org/10.1093/plphys/kiad538.
DOI: https://doi.org/10.1093/plphys/kiad538

Interpretive Summary: Every plant cell is surrounded by a sugar coat called the cell wall, which comprises Earth's major carbon sink. Essential products are made of cell walls, including food (fruit, vegetables), clothing (cotton, linen), shelter (construction materials), and fuel (wood, biofuel). Cell wall regulation is a major research topic to engineer improved plants. A class of herbicides called cellulose biosynthesis inhibitors (CBIs) are used in agriculture to kill plants by halting the production of cellulose (the major cell wall sugar). CBIs are also invaluable molecular tools used by scientists to study cell wall regulation. Recently, we discovered that long-held beliefs on CBIs are likely incorrect: instead of acting by directly targeting cellulose synthesis enzymes, they likely target completely different enzymes. We reveal conditions that allow seedlings to survive in the presence of a CBI, which should normally halt growth. Analytical techniques support our finding of an altered CBI mechanism of action. This finding raises caution in relying on CBIs to study cell wall regulation.

Technical Abstract: Cellulose biosynthesis inhibitors (CBIs) have been used for decades as agricultural herbicides and as invaluable molecular tools to study cellulose regulation, cell wall integrity sensing, and cell wall damage response pathways. It has long been assumed that CBIs inhibit cellulose biosynthesis by directly interacting cellulose synthase subunits (CESAs). However, binding of CBIs by CESA proteins has not been convincingly shown experimentally, and there are indications in the published literature that the mechanism of action of CBIs may not be limited to direct inhibition of CESAs. In this letter we highlight the discrepancies in the literature and present new experimental results that show nutrient-dependent and tissue-dependent effects of the CBI isoxaben which cannot be easily explained by direct inhibition of CESAs by isoxaben. This letter to the editor establishes the need to reconsider the use of CBIs in future studies and calls for reinterpretation of CBI-based studies as we learn more about the CBI mechanisms of action.