PCYT1A Regulates Phosphatidylcholine Homeostasis from the Inner Nuclear Membrane in Response to Membrane Stored Curvature Elastic Stress.
PCYT1A Regulates Phosphatidylcholine Homeostasis from the Inner Nuclear Membrane in Response to Membrane Stored Curvature Elastic Stress.
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DOI：
10.1016/j.devcel.2018.04.012
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发表时间：
2018-05-21
影响因子：
11.8
通讯作者：
Savage DB
中科院分区：
文献类型：
--
作者：
Haider A;Wei YC;Lim K;Barbosa AD;Liu CH;Weber U;Mlodzik M;Oras K;Collier S;Hussain MM;Dong L;Patel S;Alvarez-Guaita A;Saudek V;Jenkins BJ;Koulman A;Dymond MK;Hardie RC;Siniossoglou S;Savage DB
细胞膜和细胞器膜由决定其大小、形状和功能的磷脂(PL)的复杂混合物组成。磷脂酰胆碱(PC)是真核细胞膜中含量最丰富的磷脂，但细胞在体内如何感知和调节其水平尚不清楚。在这里，我们证明了PCYT1A，PC合成的限速酶，在酵母、苍蝇和哺乳动物细胞中是核内的，并重新定位到核膜上，以响应膜PL合成的需要。通过将成像与脂体学分析和数据驱动建模相结合，我们证明了酵母PCYT1A膜关联与膜存储曲率弹性应力估计相关。此外，这一过程发生在细胞核内，尽管核定位信号突变体可以补偿酵母和苍蝇光感受器中内源PCYT1A的损失。这些数据提示了一种古老的机制，核质PCYT1a通过感测内核膜上的表面PL填充缺陷来控制PC的动态平衡。PCYT1A催化磷脂酰胆碱(PC)合成的限速反应，PC缺乏增加细胞膜脂质储存曲率弹性(SCE)应激，PCYT1A利用新生的两亲性螺旋在核膜上检测SCE，缺乏核定位信号的突变体PCYT1A-PCYT1A缺陷细胞磷脂酰胆碱(PC)是细胞膜的主要成分。海德尔等人。结果表明，PCYT1A，PC合成的限速酶，在酵母、苍蝇和哺乳动物细胞中响应PC需求的增加而移位到内核膜上。这种PCYT1a的再定位是由膜储曲率弹性应力控制的。
Cell and organelle membranes consist of a complex mixture of phospholipids (PLs) that determine their size, shape, and function. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes, yet how cells sense and regulate its levels in vivo remains unclear. Here we show that PCYT1A, the rate-limiting enzyme of PC synthesis, is intranuclear and re-locates to the nuclear membrane in response to the need for membrane PL synthesis in yeast, fly, and mammalian cells. By aligning imaging with lipidomic analysis and data-driven modeling, we demonstrate that yeast PCYT1A membrane association correlates with membrane stored curvature elastic stress estimates. Furthermore, this process occurs inside the nucleus, although nuclear localization signal mutants can compensate for the loss of endogenous PCYT1A in yeast and in fly photoreceptors. These data suggest an ancient mechanism by which nucleoplasmic PCYT1A senses surface PL packing defects on the inner nuclear membrane to control PC homeostasis. PCYT1A catalyzes the rate-limiting reaction in phosphatidylcholine (PC) synthesis PC deficiency increases membrane lipid stored curvature elastic (SCE) stress PCYT1A uses a nascent amphipathic helix to sense SCE in the nuclear membrane PCYT1A mutants lacking a nuclear localization signal rescue PCYT1A-deficient cells Phosphatidylcholine (PC) is the major constituent of cellular membranes. Haider et al. show that PCYT1A, the rate-limiting enzyme of PC synthesis, translocates onto the inner nuclear membrane in response to increased PC need in yeast, fly, and mammalian cells. This PCYT1A re-localization is governed by membrane stored curvature elastic stress.
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影响因子：
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通讯作者：
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