Ectopic overproduction of cell wall glucan through membrane perturbation by an antifungal peptide theonellamide A in fission yeast
Year: 2026
Type: article
Abstract: 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.
Source: iScience
Institutions: The University of Tokyo, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Instituto de Biología Funcional y Genómica, Japan Women's University, Kyoto University, RIKEN Center for Sustainable Resource Science, Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Hiroshima University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
Awards: G1896100032, G2262748287, Identification of new natural products targeting cell membrane and analyses of their modes of action., Development of scarce natural products and innovative anticancer seeds, G2972037462, G3166424744, Uncovering hidden functions of intrinsic metabolites using chemical genetics and informatics, G3480869486, Omics analyses for understanding multiple functions of membrane lipids, G410571670, G4246625193, G425668148, G451917667, G523076202, G5531058919, G5539308778, G5635532810, G5711104763, G5743931246, G5967599077, G6033112984, Innovative chemical genetics on novel function of endogenous metabolites, G6728930308, G6731467812, Chemical genetics for understanding structure and function of cell membranes, G7330179772, 古代説話における諸寺縁起の研究, G7863371703, G8497050386, G9000848794
OpenAlex ID: W7215030358