Alleles Causing Resistance to Isoxaben and Flupoxam Highlight the Significance of Transmembrane Domains for CESA Protein Function

The cellulose synthase (CESA) proteins in Arabidopsis play an essential role in the production of cellulose in the cell walls. Herbicides such as isoxaben and flupoxam specifically target this production process and are prominent cellulose biosynthesis inhibitors (CBIs). Forward genetic screens in Arabidopsis revealed that mutations that can result in varying degrees of resistance to either isoxaben or flupoxam CBI can be attributed to single amino acid substitutions in primary wall CESAs. Missense mutations were almost exclusively present in the predicted transmembrane regions of CESA1, CESA3, and CESA6. Resistance to isoxaben was also conferred by modification to the catalytic residues of CESA3. This resulted in cellulose deficient phenotypes characterized by reduced crystallinity and dwarfism. However, mapping of mutations to the transmembrane regions also lead to growth phenotypes and altered cellulose crystallinity phenotypes. These results provide further genetic evidence supporting the involvement of CESA transmembrane regions in cellulose biosynthesis.