Abstract
Here, biophysical properties of membranes enriched in three metabolically related sterols are analyzed both in vitro and in vivo. Unlike cholesterol and ergosterol, the common metabolic precursor zymosterol is unable to induce the formation of a liquid ordered (lo) phase in model lipid membranes and can easily accommodate in a gel phase. As a result, Zym has a marginal ability to modulate the passive membrane permeability of lipid vesicles with different compositions, contrary to cholesterol and ergosterol. Using fluorescence-lifetime imaging microscopy of an aminostyryl dye in living mammalian and yeast cells we established a close parallel between sterol-dependent membrane biophysical properties in vivo and in vitro. This approach unraveled fundamental differences in yeast and mammalian plasma membrane organization. It is often suggested that, in eukaryotes, areas that are sterol-enriched are also rich in sphingolipids, constituting highly ordered membrane regions. Our results support that while cholesterol is able to interact with saturated lipids, ergosterol seems to interact preferentially with monounsaturated phosphatidylcholines. Taken together, we show that different eukaryotic kingdoms developed unique solutions for the formation of a sterol-rich plasma membrane, a common evolutionary trait that accounts for sterol structural diversity.
Highlights
Ergosterol (Erg) and cholesterol (Chol) are the major sterols in yeast and mammalian cell membrane, respectively
Zymosterol is a biosynthetic precursor of both cholesterol, the major sterol in the plasma membrane of animal cells, and ergosterol, the major sterol in the plasma membrane of fungi
In order to directly evaluate the ability of Zym to induce the coexistence of liquid/liquid domains, Erg or Zym were incorporated into Giant unilamellar vesicles (GUVs) containing equimolar ratios of the saturated lipid DPPC and the unsaturated lipid DOPC, and their behaviors were compared to that of the DOPC/DPPC binary mixture
Summary
Ergosterol (Erg) and cholesterol (Chol) are the major sterols in yeast (fungi) and mammalian (animal) cell membrane, respectively. Erg and Chol have been considered crucial for the formation of a subset of membrane lipid domains described as being in a liquid ordered (lo) phase, due to their ability to establish tight interactions with sphingolipids (Simons and Vaz, 2004; Klose et al, 2010) Both Chol and Erg form lo phases, their respective two kingdoms present fundamental differences in their membrane lipid organization, namely the transient nature and nanoscopic scale of the lipid domains in mammalian cells (Sezgin et al, 2017) versus stable large membrane compartments in yeast (Malinsky and Opekarova, 2016; Athanasopoulos et al, 2019; Zahumensky and Malinsky, 2019). Zymosterol is a biosynthetic precursor of both cholesterol, the major sterol in the plasma membrane of animal cells, and ergosterol, the major sterol in the plasma membrane of fungi
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