Inhibition of Glycosphingolipid Biosynthesis Induces Cytokinesis Failure

TY - JOUR

T1 - Inhibition of Glycosphingolipid Biosynthesis Induces Cytokinesis Failure

AU - Atilla-Gokcumen, G. E.

AU - Bedigian, A. V.

AU - Sasse, S.

AU - Eggert, U. S.

PY - 2011/7/6

Y1 - 2011/7/6

N2 - 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.

AB - 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.

U2 - 10.1021/ja202804b

DO - 10.1021/ja202804b

M3 - Article

SN - 0002-7863

VL - 133

SP - 10010

EP - 10013

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 26

ER -