Inactivation of the C-elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope
Inactivation of the C-elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope
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DOI：
10.1242/jcs.044743
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发表时间：
2009-06-15
影响因子：
4
通讯作者：
Cohen-Fix, Orna
中科院分区：
文献类型：
--
作者：
Golden, Andy;Liu, Jun;Cohen-Fix, Orna
核膜(NE)是一种动态结构，在细胞周期中经历生长、分解和重组三个阶段。在酵母中，通过使磷脂(一种磷脂酸磷酸水解酶)的酵母同系物失活来改变脂质的合成，会导致外周内质网的解体和核的异常形状。这些结果表明，脂质代谢有助于去甲肾上腺素的动态；然而，由于酵母经历闭合有丝分裂，这些观察结果与高等真核生物的相关性尚不清楚。在哺乳动物中，脂类与脂肪组织分化、胰岛素抵抗、脂肪储存和肥胖有关，但由于脂类水平变化而导致的潜在细胞缺陷尚不清楚。在这里，我们确定了秀丽隐杆线虫的脂类同系物(LPIN-1)，并研究了它对NE动力学的影响。我们发现，RNAi下调LPIN-1导致外周内质网出现膜片和其他异常结构。此外，lpin-1 RNAi还导致NE断裂、染色体异常分离和核形态不规则。这些结果揭示了脂类对后生动物细胞过程的影响，并表明脂质合成在去甲肾上腺素动力学中具有作用。
The nuclear envelope (NE) is a dynamic structure, undergoing periods of growth, breakdown and reassembly during the cell cycle. In yeast, altering lipid synthesis by inactivating the yeast homolog of lipin, a phosphatidic acid phosphohydrolase, leads to disorganization of the peripheral ER and abnormal nuclear shape. These results suggest that lipid metabolism contributes to NE dynamics; however, since yeast undergo closed mitosis, the relevance of these observations to higher eukaryotes is unclear. In mammals, lipin has been implicated in adipose tissue differentiation, insulin resistance, lipid storage and obesity, but the underlying cellular defects caused by altering lipin levels are not known. Here, we identify the Caenorhabditis elegans lipin homolog (LPIN-1) and examine its affect on NE dynamics. We find that downregulating LPIN-1 by RNAi results in the appearance of membrane sheets and other abnormal structures in the peripheral ER. Moreover, lpin-1 RNAi causes defects in NE breakdown, abnormal chromosome segregation and irregular nuclear morphology. These results uncover cellular processes affected by lipin in metazoa, and suggest that lipid synthesis has a role in NE dynamics.