Targeting Cholesterol in a Liquid-Disordered Environment by Theonellamides Modulates Cell Membrane Order and Cell Shape. Issue 5 (21st May 2015)

• Record Type: Journal Article
• Authors: Arita, Yuko; Nishimura, Shinichi; Ishitsuka, Reiko; Kishimoto, Takuma; Ikenouchi, Junichi; Ishii, Kumiko; Umeda, Masato; Matsunaga, Shigeki; Kobayashi, Toshihide; Yoshida, Minoru
• Is Part Of: Chemistry & biology. Volume 22:Issue 5(2015)
• Page Start: 604
• Page End: 610
• Publication Date: 2015-05-21
• Subjects: Biochemistry -- Periodicals; 540
• DOI: 10.1016/j.chembiol.2015.04.011
• Languages: English
• ISSNs: 1074-5521

Abstract

Summary: Roles of lipids in the cell membrane are poorly understood. This is partially due to the lack of methodologies, for example, tool chemicals that bind to specific membrane lipids and modulate membrane function. Theonellamides (TNMs), marine sponge-derived peptides, recognize 3β-hydroxysterols in lipid membranes and induce major morphological changes in cultured mammalian cells through as yet unknown mechanisms. Here, we show that TNMs recognize cholesterol-containing liquid-disordered domains and induce phase separation in model lipid membranes. Modulation of membrane order was also observed in living cells following treatment with TNM-A, in which cells shrank considerably in a cholesterol-, cytoskeleton-, and energy-dependent manner. These findings present a previously unrecognized mode of action of membrane-targeting natural products. Meanwhile, we demonstrated the importance of membrane order, which is maintained by cholesterol, for proper cell morphogenesis. Graphical Abstract: Highlights: TNMs, marine-derived peptides, recognize cholesterol in liquid-disordered domains TNMs modulate membrane order in model and cellular membranes Cells shrink in a cholesterol-dependent manner after TNM-A treatment The membrane order maintained by cholesterol is important for cell morphogenesis Abstract : Arita et al. report that theonellamides (TNMs), marine-derived peptides, exhibit a previously unrecognized mode of action of membrane-targeting natural products. Using TNMs as tools, the membrane order, which is maintained by cholesterol, was revealed to be important for proper cell morphogenesis.