Removal of Stomatin, a Membrane-Associated Cell Division Protein, Results in Specific Cellular Lipid Changes.

Removal of Stomatin, a Membrane-Associated Cell Division Protein, Results in Specific Cellular Lipid Changes.
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DOI:
10.1021/jacs.2c07907
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发表时间:
2022-10-05
影响因子:
15
通讯作者:
Eggert, Ulrike S.
Eggert, Ulrike S.
中科院分区:
化学1区
文献类型:
--
作者:
Dona, Federico;Ozbalci, Cagakan;Paquola, Andrea;Ferrentino, Federica;Terry, Stephen J.;Storck, Elisabeth M.;Wang, Gaoge;Eggert, Ulrike S.

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脂类是所有细胞的关键成分,表达成千上万种不同的脂类。在大多数情况下,还不知道为什么细胞会合成如此多样化的脂体,也不知道是什么调节了它们的新陈代谢。虽然已知分裂细胞专门调节它们的脂质含量,并且成功分裂需要正确的脂类补体,但脂类如何与细胞分裂机制相联系尚不清楚。在此,我们报道了膜蛋白口腔蛋白参与了细胞分裂的胞质分裂步骤。虽然它不是一种脂类生物合成酶,但气孔蛋白的耗尽会导致细胞改变其脂体。这些变化包括特定的脂类,如乙醚类脂类,以及脂类家族,如磷脂酰胆碱。外源性磷脂酰胆碱的加入可以修复由口腔素引起的缺陷。这些数据表明,口腔素与脂类代谢有关。Stomatin与质膜有多个接触,我们确定了它在细胞分裂中所需的位置,以及相关的脂类变化。我们还表明,气孔在质膜上的流动性在分裂过程中发生变化,进一步支持了膜脂和这种新发现的细胞分裂蛋白之间高度调控的物理相互作用的要求。
Lipids are key constituents of all cells, which express thousands of different lipid species. In most cases, it is not known why cells synthesize such diverse lipidomes, nor what regulates their metabolism. Although it is known that dividing cells specifically regulate their lipid content and that the correct lipid complement is required for successful division, it is unclear how lipids connect with the cell division machinery. Here, we report that the membrane protein stomatin is involved in the cytokinesis step of cell division. Although it is not a lipid biosynthetic enzyme, depletion of stomatin causes cells to change their lipidomes. These changes include specific lipid species, like ether lipids, and lipid families like phosphatidylcholines. Addition of exogenous phosphatidylcholines rescues stomatin-induced defects. These data suggest that stomatin interfaces with lipid metabolism. Stomatin has multiple contacts with the plasma membrane and we identify which sites are required for its role in cell division, as well as associated lipid shifts. We also show that stomatin’s mobility on the plasma membrane changes during division, further supporting the requirement for a highly regulated physical interaction between membrane lipids and this newly identified cell division protein.
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