Ceramide structure dictates glycosphingolipid nanodomain assembly and function
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Ceramide structure dictates glycosphingolipid nanodomain assembly and function. / Arumugam, Senthil; Schmieder, Stefanie; Pezeshkian, Weria; Becken, Ulrike; Wunder, Christian; Chinnapen, Dan; Ipsen, John Hjort; Kenworthy, Anne K.; Lencer, Wayne; Mayor, Satyajit; Johannes, Ludger.
I: Nature Communications, Bind 12, Nr. 1, 3675, 16.06.2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Ceramide structure dictates glycosphingolipid nanodomain assembly and function
AU - Arumugam, Senthil
AU - Schmieder, Stefanie
AU - Pezeshkian, Weria
AU - Becken, Ulrike
AU - Wunder, Christian
AU - Chinnapen, Dan
AU - Ipsen, John Hjort
AU - Kenworthy, Anne K.
AU - Lencer, Wayne
AU - Mayor, Satyajit
AU - Johannes, Ludger
PY - 2021/6/16
Y1 - 2021/6/16
N2 - 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. Gangliosides such as GM1 present in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. Here the authors show that the acyl chain structure of GM1 determines the establishment of nanodomains when actively clustered by actin, which depended on membrane cholesterol and phosphatidylserine or superimposed by the GM1-binding bacterial cholera toxin.
AB - 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. Gangliosides such as GM1 present in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. Here the authors show that the acyl chain structure of GM1 determines the establishment of nanodomains when actively clustered by actin, which depended on membrane cholesterol and phosphatidylserine or superimposed by the GM1-binding bacterial cholera toxin.
KW - GPI-ANCHORED PROTEINS
KW - PLASMA-MEMBRANE
KW - CHOLERA-TOXIN
KW - MOLECULAR-DYNAMICS
KW - CORTICAL ACTIN
KW - PHASE-SEPARATION
KW - FORCE-FIELD
KW - RECEPTOR
KW - GM1
KW - ORGANIZATION
U2 - 10.1038/s41467-021-23961-9
DO - 10.1038/s41467-021-23961-9
M3 - Journal article
C2 - 34135326
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3675
ER -
ID: 316749976