Inefficient development of syncytiotrophoblasts in the Atp11a-deficient mouse placenta.
Inefficient development of syncytiotrophoblasts in the Atp11a-deficient mouse placenta.
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atp11a缺陷小鼠胎盘中合胞滋养细胞的低效发育。
DOI：
10.1073/pnas.2200582119
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发表时间：
2022-05-03
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
质膜由脂质双层组成，其中磷脂酰丝氨酸（PtdSer）通过将PtdSer从外小叶转位至内小叶的翻转酶的作用而被限制于内小叶。两种P4-ATP酶（ATP 11 A和ATP 11 C）在质膜上作为翻转酶工作。在这里，我们报告说，小鼠胎盘只表达ATP 11 A，和ATP 11 A缺陷的小鼠胚胎在胚胎发育过程中死亡，由于胎盘迷路中的合胞体滋养细胞的形成效率低下。翻转酶无效突变使人绒毛膜癌BeWo细胞失活，将PtdSer转运到内叶并进行细胞融合。这些发现突出了翻转酶调节细胞融合的磷脂分布的重要性，至少在滋养层融合。P4-ATP酶ATP 11 A和ATP 11 C在质膜上起翻转酶的作用，将磷脂酰丝氨酸从外叶转位到内叶。我们在此证明，Atp 11 a缺陷小鼠胚胎死亡约E14.5薄壁心室。然而，心肌细胞或外胚层特异性Atp 11 a缺失并不影响小鼠的发育或死亡率。ATP 11 C可能在胚胎中的大多数细胞类型中补偿了ATP 11 A的功能。另一方面，Atp 11 a，而不是Atp 11 c，在小鼠胎盘中表达，Atp 11 a无效突变引起胎盘层发育不良，TUNEL阳性灶的数量增加。免疫组化和电子显微镜显示，在Atp 11 a无效胎盘的未融合的滋养细胞的一个混乱的胎盘层。人胎盘绒毛膜癌BeWo细胞表达ATP 11 A和ATP 11 C基因。缺乏ATP 11 A和ATP 11 C消除了BeWo细胞翻转磷脂酰丝氨酸和融合的能力，当用毛喉素处理时。这些结果表明，在胎盘发育的合体滋养细胞的形成中，质膜翻转酶起着重要的作用。
Plasma membranes are composed of a lipid bilayer in which phosphatidylserine (PtdSer) is confined to the inner leaflet by the action of flippase that translocates PtdSer from the outer to inner leaflets. Two P4-ATPases (ATP11A and ATP11C) work as flippase at plasma membranes. Here, we report that the mouse placenta expresses only ATP11A, and Atp11a-deficient mouse embryos die during embryogenesis due to inefficient formation of syncytiotrophoblasts in the placental labyrinth. The flippase-null mutation inactivates human choriocarcinoma BeWo cells to translocate PtdSer into the inner leaflet and undergo cell fusion. These findings highlight the importance of flippase to regulate the distribution of phospholipids for cell fusion, at least in trophoblast fusion. The P4-ATPases ATP11A and ATP11C function as flippases at the plasma membrane to translocate phosphatidylserine from the outer to the inner leaflet. We herein demonstrated that Atp11a-deficient mouse embryos died at approximately E14.5 with thin-walled heart ventricles. However, the cardiomyocyte- or epiblast-specific Atp11a deletion did not affect mouse development or mortality. ATP11C may have compensated for the function of ATP11A in most of the cell types in the embryo. On the other hand, Atp11a, but not Atp11c, was expressed in the mouse placenta, and the Atp11a-null mutation caused poor development of the labyrinthine layer with an increased number of TUNEL-positive foci. Immunohistochemistry and electron microscopy revealed a disorganized labyrinthine layer with unfused trophoblasts in the Atp11a-null placenta. Human placenta-derived choriocarcinoma BeWo cells expressed the ATP11A and ATP11C genes. A lack of ATP11A and ATP11C eliminated the ability of BeWo cells to flip phosphatidylserine and fuse when treated with forskolin. These results indicate that flippases at the plasma membrane play an important role in the formation of syncytiotrophoblasts in placental development.
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影响因子：
3.8
作者：
Nagai, A.;Takebe, K.;Iwanaga, T.
通讯作者：
Iwanaga, T.
影响因子：
2.6
作者：
Hayashi, Shigemi;Lewis, Paula;McMahon, Andrew P.
通讯作者：
McMahon, Andrew P.
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
DOI：
10.1073/pnas.0902925106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Dupressoir, Anne;Vernochet, Cecile;Heidmann, Thierry
通讯作者：
Heidmann, Thierry
影响因子：
0.7
作者：
Hu, Dong;Cross, James C.
通讯作者：
Cross, James C.