Ectopic overproduction of cell wall glucan through membrane perturbation by an antifungal peptide theonellamide A in fission yeast

This is the authors' abstract. We don't add key points for this paper.

Ergosterol has multiple functions in filamentous fungi and yeasts, although only a part of the functions seems to be understood. An antifungal peptide, theonellamide A (TNM-A) induces drastic morphological changes in fission yeast by targeting plasma membrane ergosterol. TNM-A induces overproduction and accumulation of cell wall glucan at growing tips and septum through a yet unknown mechanism. Here, we show that TNM-A causes accumulation of 1,3-β-glucan at cell-polarity sites, not by increased activity of 1,3-β-glucan synthase, but by an increased, persistent localization of the glucan synthases. Screening based on subcellular localization of proteins suggested the involvement of the Rho family GTPase Cdc42, a master regulator of cell polarity. In agreement, TNM-A increased active Cdc42 and enhanced the membrane trafficking of glucan synthases. In conclusion, our chemical genetics analyses using TNM-A suggest that membrane ergosterol regulates the Cdc42 activity, which further regulates the localization of glucan synthases and cell wall biosynthesis.