μ1A-adaptin-deficient mice:: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors
μ1A-adaptin-deficient mice:: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors
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DOI：
10.1093/emboj/19.10.2193
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发表时间：
2000-05-15
期刊：
影响因子：
11.4
通讯作者：
Schu, P
中科院分区：
文献类型：
--
作者：
Meyer, C;Zizioli, D;Schu, P
异源四聚体AP-1复合物参与在反式高尔基体网络（TGN）处网格蛋白包被的囊泡的形成，并与货物分子的细胞质尾部中的分选信号相互作用。小鼠mu 1A-适应素基因的靶向破坏在第13.5天导致胚胎死亡。在mu 1A-适应素缺陷的细胞中，剩余的AP-1适应素不与TGN结合。极化上皮细胞是mu 1A-适应素缺陷胚胎中唯一显示出γ-适应素与膜结合的细胞，表明上皮特异性AP-1B复合物的形成，并证明没有额外的mu 1A同源物。甘露糖6-磷酸受体是经由AP-1-网格蛋白包被的囊泡离开TGN的货物分子。甘露糖6-磷酸受体MPR 46和MPR 300在mu 1A缺陷细胞中的稳态分布以TGN为代价转移到内体，MPR 46不能从内体再循环回到TGN，表明AP-1是受体逆行内体到TGN转运所需的。
The heterotetrameric AP-1 complex is involved in the formation of clathrin-coated vesicles at the trans-Golgi network (TGN) and interacts with sorting signals in the cytoplasmic tails of cargo molecules. Targeted disruption of the mouse mu 1A-adaptin gene causes embryonic lethality at day 13.5. In cells deficient in mu 1A-adaptin the remaining AP-1 adaptins do not bind to the TGN. Polarized epithelial cells are the only cells of mu 1A-adaptin-deficient embryos that show gamma-adaptin binding to membranes, indicating the formation of an epithelial specific AP-1B complex and demonstrating the absence of additional mu 1A homologs. Mannose 6-phosphate receptors are cargo molecules that exit the TGN via AP-l-clathrin-coated vesicles. The steady-state distribution of the mannose 6-phosphate receptors MPR46 and MPR300 in mu 1A-deficient cells is shifted to endosomes at the expense of the TGN, MPR46 fails to recycle back from the endosome to the TGN, indicating that AP-1 is required for retrograde endosome to TGN transport of the receptor.