PDF(Pubmed)
Abstract：
Failure to reorganize the endoplasmic reticulum (ER) in mitosis results in chromosome missegregation. Here, we show that accurate chromosome segregation in human cells requires cell cycle-regulated ER membrane production. Excess ER membranes increase the viscosity of the mitotic cytoplasm to physically restrict chromosome movements, which impedes the correction of mitotic errors leading to the formation of micronuclei. Mechanistically, we demonstrate that the protein phosphatase CTDNEP1 counteracts mTOR kinase to establish a dephosphorylated pool of the phosphatidic acid phosphatase lipin 1 in interphase. CTDNEP1 control of lipin 1 limits the synthesis of fatty acids for ER membrane biogenesis in interphase that then protects against chromosome missegregation in mitosis. Thus, regulation of ER size can dictate the biophysical properties of mitotic cells, providing an explanation for why ER reorganization is necessary for mitotic fidelity. Our data further suggest that dysregulated lipid metabolism is a potential source of aneuploidy in cancer cells.
摘要：
在有丝分裂中未能重组内质网(ER)导致染色体错误分离。这里,我们表明，人类细胞中准确的染色体分离需要细胞周期调节的ER膜的产生。过量的ER膜增加有丝分裂细胞质的粘度，以物理限制染色体运动，这阻碍了有丝分裂错误的纠正，导致微核的形成。机械上,我们证明，蛋白磷酸酶CTDNEP1抵消mTOR激酶，以建立间期磷脂酸磷酸酶lipin1的去磷酸化池。CTDNEP1对lipin1的控制限制了间期中ER膜生物发生的脂肪酸的合成，然后防止有丝分裂中的染色体错误分离。因此，ER大小的调节可以决定有丝分裂细胞的生物物理特性，提供了为什么ER重组对于有丝分裂保真度是必要的解释。我们的数据进一步表明，脂质代谢失调是癌细胞非整倍体的潜在来源。
