Dividing cells regulate their lipid composition and localization.
Dividing cells regulate their lipid composition and localization.
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DOI：
10.1016/j.cell.2013.12.015
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发表时间：
2014-01-30
期刊：
影响因子：
64.5
通讯作者：
Eggert US
中科院分区：
文献类型：
--
作者：
Atilla-Gokcumen GE;Muro E;Relat-Goberna J;Sasse S;Bedigian A;Coughlin ML;Garcia-Manyes S;Eggert US
虽然细胞分裂过程中会发生大量的膜重排，但人们对脂质在这一过程中可能发挥的特定作用知之甚少。我们报道了脂质体随着细胞周期的变化而变化。基于LC-MS的脂质分析显示，11种具有特定化学结构的脂质在分裂细胞中积累。使用原子力显微镜，我们证明了活的分裂细胞和他们的孤立的脂质相对于nondividing细胞的机械性能的差异。同时，脂质生物合成酶的系统性RNAi敲除鉴定了分裂所需的酶，其与分裂细胞中积累的脂质高度相关。我们表明，细胞特异性地调节脂质定位到中间体，基于膜的结构，其中发生裂解。我们的结论是，细胞在分裂过程中积极调节和调节其脂质组成和定位，信号和结构的作用可能。这项工作对脂质在基础生物学中的积极和持续参与具有更广泛的意义。对分裂细胞和中间体进行系统、全面的脂质分析AFM显示分裂细胞及其脂质具有特定的物理性质脂质生物合成酶的筛选揭示了分裂所需的23个基因扰动的脂质水平改变了肌动蛋白细胞骨架和细胞硬度脂质谱在细胞分裂期间发生显著变化，显示出独特的物理性质和定位模式，表明脂质群体对分裂过程的结构和信号作用。
Although massive membrane rearrangements occur during cell division, little is known about specific roles that lipids might play in this process. We report that the lipidome changes with the cell cycle. LC-MS-based lipid profiling shows that 11 lipids with specific chemical structures accumulate in dividing cells. Using AFM, we demonstrate differences in the mechanical properties of live dividing cells and their isolated lipids relative to nondividing cells. In parallel, systematic RNAi knockdown of lipid biosynthetic enzymes identified enzymes required for division, which highly correlated with lipids accumulated in dividing cells. We show that cells specifically regulate the localization of lipids to midbodies, membrane-based structures where cleavage occurs. We conclude that cells actively regulate and modulate their lipid composition and localization during division, with both signaling and structural roles likely. This work has broader implications for the active and sustained participation of lipids in basic biology. Systematic, comprehensive lipid analyses in dividing cells and midbodies AFM shows dividing cells and their lipids have specific physical properties Screen of lipid biosynthetic enzymes reveals 23 genes required for division Perturbing lipid levels alters actin cytoskeleton and cell stiffness Lipid profiles change significantly during cell division, showing distinctive physical properties and localization patterns that suggest structural and signaling contributions from lipid populations to the process of division.
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