RRC ID 65691
Author Arumugam S, Schmieder S, Pezeshkian W, Becken U, Wunder C, Chinnapen D, Ipsen JH, Kenworthy AK, Lencer W, Mayor S, Johannes L.
Title Ceramide structure dictates glycosphingolipid nanodomain assembly and function.
Journal Nat Commun
Abstract Gangliosides in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. How gangliosides are dynamically organized and how they respond to ligand binding is poorly understood. Using fluorescence anisotropy imaging of synthetic, fluorescently labeled GM1 gangliosides incorporated into the plasma membrane of living cells, we found that GM1 with a fully saturated C16:0 acyl chain, but not with unsaturated C16:1 acyl chain, is actively clustered into nanodomains, which depends on membrane cholesterol, phosphatidylserine and actin. The binding of cholera toxin B-subunit (CTxB) leads to enlarged membrane domains for both C16:0 and C16:1, owing to binding of multiple GM1 under a toxin, and clustering of CTxB. The structure of the ceramide acyl chain still affects these domains, as co-clustering with the glycosylphosphatidylinositol (GPI)-anchored protein CD59 occurs only when GM1 contains the fully saturated C16:0 acyl chain, and not C16:1. Thus, different ceramide species of GM1 gangliosides dictate their assembly into nanodomains and affect nanodomain structure and function, which likely underlies many endogenous cellular processes.
Volume 12(1)
Pages 3675
Published 2021-6-16
DOI 10.1038/s41467-021-23961-9
PII 10.1038/s41467-021-23961-9
PMID 34135326
PMC PMC8209009
MeSH Actins / chemistry CD59 Antigens / chemistry Cell Membrane / chemistry* Cell Membrane / drug effects Ceramides / chemistry* Cholera Toxin / chemistry Cholera Toxin / pharmacology Cholesterol / chemistry G(M1) Ganglioside / chemistry Glycosphingolipids / chemistry Glycosylphosphatidylinositols / chemistry Models, Biological Molecular Dynamics Simulation Phosphatidylserines / chemistry
IF 12.121
Human and Animal Cells GM95(RCB1026)