Clathrin adaptor AP-2 is essential for early embryonal development
Clathrin adaptor AP-2 is essential for early embryonal development
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DOI：
10.1128/mcb.25.21.9318-9323.2005
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发表时间：
2005-11-01
影响因子：
5.3
通讯作者：
Ohno, H
中科院分区：
文献类型：
--
作者：
Mitsunari, T;Nakatsu, F;Ohno, H
异源四聚体衔接蛋白（AP）复合物AP-1，AP-2，AP-3和AP-4在高尔基体后运输途径中的运输囊泡形成和货物分选中起关键作用。对培养的哺乳动物细胞的研究表明，AP-2介导质膜受体亚群的快速内吞作用。为了确定这种功能是否在整个哺乳动物生物体中是必不可少的，我们在小鼠中对编码AP-2的mu 2亚基的基因进行了靶向破坏。我们发现mu 2杂合突变小鼠是可行的，并有一个明显的正常表型。与此相反，没有mu 2纯合子突变体胚胎中发现的囊胚从杂交杂合子，表明mu 2缺陷的胚胎死亡前3.5天交配后（E3.5）。这些结果表明，AP-2是胚胎早期发育所必需的，这可能是由于其对细胞活力的需求。
The heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, AP-3, and AP-4 play key roles in transport vesicle formation and cargo sorting in post-Golgi trafficking pathways. Studies on cultured mammalian cells have shown that AP-2 mediates rapid endocytosis of a subset of plasma membrane receptors. To determine whether this function is essential in the context of a whole mammalian organism, we carried out targeted disruption of the gene encoding the mu 2 subunit of AP-2 in the mouse. We found that mu 2 heterozygous mutant mice were viable and had an apparently normal phenotype. In contrast, no mu 2 homozygous mutant embryos were identified among blastocysts from intercrossed heterozygotes, indicating that mu 2-deficient embryos die before day 3.5 postcoitus (E3.5). These results indicate that AP-2 is indispensable for early embryonic development, which might be due to its requirement for cell viability.