Lipid cosorting mediated by shiga toxin induced tubulation.
To maintain cell membrane homeostasis, lipids must be dynamically redistributed during the formation of transport intermediates, but the mechanisms driving lipid sorting are not yet fully understood. Lowering sphingolipid concentration can reduce the bending energy of a membrane, and this effect could account for sphingolipid depletion along the retrograde pathway. However, sphingolipids and cholesterol are enriched along the anterograde pathway, implying that other lipid sorting mechanisms, such as protein-mediated sorting, can dominate. To characterize the influence of protein binding on the lipid composition of highly curved membranes, we studied the interactions of the B-subunit of Shiga toxin (STxB) with giant unilamellar vesicles containing its glycosphingolipid receptor [globotriaosylceramide (Gb3)]. STxB binding induced the formation of tubular membrane invaginations, and fluorescence microscopy images of these highly curved membranes were consistent with co-enrichment of Gb3 and sphingolipids. In agreement with theory, sorting was stronger for membrane compositions close to demixing. These results strongly support the hypothesis that proteins can indirectly mediate the sorting of lipids into highly curved transport intermediates via interactions between lipids and the membrane receptor of the protein.
Safouane
Mahassine
M
Institut Curie, Centre de Recherche, Membrane and Cell Functions Group, CNRS UMR168, Physico-Chimie Curie, Université Pierre et Marie Curie, 75248 Paris Cedex 05, France.
Berland
Ludwig
L
Callan-Jones
Andrew
A
Sorre
Benoit
B
Römer
Winfried
W
Johannes
Ludger
L
Toombes
Gilman E S
GE
Bassereau
Patricia
P
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D011485:Protein Binding; D022621:Shiga Toxin / Q000737:chemistry / Q000378:metabolism*; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*; D014281:Trihexosylceramides / Q000737:chemistry / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism
D013107:Sphingolipids; D014281:Trihexosylceramides; D053835:Unilamellar Liposomes; C018549:globotriaosylceramide; D022621:Shiga Toxin