Dana-Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Am Chem Soc. 2011 Jul 6;133(26):10010-3. doi: 10.1021/ja202804b. Epub 2011 Jun 14.
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.
尽管细胞在胞质分裂过程中会经历剧烈的形态变化，但细胞膜和脂质的作用还知之甚少。我们报告说，葡萄糖神经酰胺合酶（GCS）的失活，无论是通过 RNAi 还是小分子 PPMP，都会导致分裂沟内陷失败。使用基于质谱的全局脂质分析，我们确定了由于 GCS 抑制而增强或耗尽的个别脂质。我们表明，GCS 抑制导致肌动蛋白和 ERM 蛋白的定位错误，ERM 蛋白是将质膜与肌动蛋白皮质连接的关键细胞骨架蛋白。我们的数据表明，神经酰胺参与调节膜和皮质之间的相互作用。
