Acute manipulation of diacylglycerol reveals roles in nuclear envelope assembly & endoplasmic reticulum morphology.
Acute manipulation of diacylglycerol reveals roles in nuclear envelope assembly & endoplasmic reticulum morphology.
复制标题
DOI：
10.1371/journal.pone.0051150
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Larijani B
中科院分区：
文献类型：
--
作者：
Domart MC;Hobday TM;Peddie CJ;Chung GH;Wang A;Yeh K;Jethwa N;Zhang Q;Wakelam MJ;Woscholski R;Byrne RD;Collinson LM;Poccia DL;Larijani B
细胞膜的功能和形态密切相关，不仅取决于它们的蛋白质含量，还取决于构成它们的脂质的全部成分。由于缺乏有关内膜脂质不对称性的体内数据，有人认为是马达、支架蛋白或整合膜蛋白而不是非层状双层脂质（例如二酰基甘油（DAG））负责细胞器的成形、局部膜曲率和融合。直接改变此类脂质水平的影响仍未得到研究。二酰基甘油 (DAG) 是一种有据可查的第二信使。在这里，我们展示了 DAG 的两个额外保守功能：细胞器形态中的结构作用，以及融合所需的局部极端膜曲率的作用，而仅靠蛋白质是不够的。相关光学和电子显微镜以及 3D 重建显示，急性和诱导性 DAG 耗竭导致核膜 (NE) 在有丝分裂时无法重组，并且 ER 无法重组为多层片。值得注意的是，耗尽的细胞在没有完整 NE 的情况下分裂，除非被 1,2 或 1,3 DAG 拯救，否则很快就会死亡。通过将酶显微注射到棘皮动物卵和胚胎中来减弱 DAG 水平也会导致 ER 形态和核膜融合的改变。我们的研究结果表明，DAG 是哺乳动物和棘皮动物细胞细胞器形态的体内调节剂，表明在后口动物超门中保守的基本作用。
The functions and morphology of cellular membranes are intimately related and depend not only on their protein content but also on the repertoire of lipids that comprise them. In the absence of in vivo data on lipid asymmetry in endomembranes, it has been argued that motors, scaffolding proteins or integral membrane proteins rather than non-lamellar bilayer lipids such as diacylglycerol (DAG), are responsible for shaping of organelles, local membrane curvature and fusion. The effects of direct alteration of levels of such lipids remain predominantly uninvestigated. Diacylglycerol (DAG) is a well documented second messenger. Here we demonstrate two additional conserved functions of DAG: a structural role in organelle morphology, and a role in localised extreme membrane curvature required for fusion for which proteins alone are insufficient. Acute and inducible DAG depletion results in failure of the nuclear envelope (NE) to reform at mitosis and reorganisation of the ER into multi-lamellar sheets as revealed by correlative light and electron microscopy and 3D reconstructions. Remarkably, depleted cells divide without a complete NE, and unless rescued by 1,2 or 1,3 DAG soon die. Attenuation of DAG levels by enzyme microinjection into echinoderm eggs and embryos also results in alterations of ER morphology and nuclear membrane fusion. Our findings demonstrate that DAG is an in vivo modulator of organelle morphology in mammalian and echinoderm cells, indicating a fundamental role conserved across the deuterostome superphylum.
登录
查看更多内容
影响因子：
4
作者：
Ma, Yan;Cai, Shang;Zhang, Chuanmao
通讯作者：
Zhang, Chuanmao
影响因子：
3.7
作者：
Dumas F;Byrne RD;Vincent B;Hobday TM;Poccia DL;Larijani B
通讯作者：
Larijani B
影响因子：
3.7
作者：
Knorr RL;Dimova R;Lipowsky R
通讯作者：
Lipowsky R
影响因子：
4.8
作者：
Barona, T;Byrne, RD;Poccia, DL
通讯作者：
Poccia, DL
影响因子：
4.1
作者：
Sánchez-Piñera, P;Micol, V;Gómez-Fernández, JC
通讯作者：
Gómez-Fernández, JC