title: Inhibition of glycosphingolipid biosynthesis induces cytokinesis failure.
abstract: Although cells undergo dramatic shape changes during cytokinesis, the role of the plasma membrane and lipids is poorly understood. We report that inactivation of glucosyl ceramide synthase (GCS), either by RNAi or with the small molecule PPMP, causes failure of cleavage furrow ingression. Using mass-spectrometry-based global lipid profiling, we identify individual lipids that are enhanced or depleted due to GCS inhibition. We show that GCS inhibition results in the mislocalization of actin and the ERM proteins, key cytoskeletal proteins that connect the plasma membrane to the actin cortex. Our data suggest that ceramides participate in mediating the interactions between the membrane and the cortex.
authors.affiliation: Dana-Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Atilla-Gokcumen
authors.forename: A V
authors.initials: AV
authors.lastname: Bedigian
authors.forename: S
authors.initials: S
authors.lastname: Sasse
authors.forename: U S
authors.initials: US
authors.lastname: Eggert
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D048749:Cytokinesis / Q000187:drug effects*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D006028:Glycosphingolipids / Q000096:biosynthesis*; D006367:HeLa Cells; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D034622:RNA Interference; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013107:Sphingolipids / Q000494:pharmacology
chemical_list: C095823:1-phenyl-2-palmitoylamino-3-morpholino-1-propanol; D006028:Glycosphingolipids; D009025:Morpholines; D054852:Small Molecule Libraries; D013107:Sphingolipids; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase