The Golgi‐localized, gamma‐ear containing, ADP‐ribosylation factor‐binding proteins (GGAs 1, 2, and 3) are multidomain proteins that bind mannose 6‐phosphate receptors (MPRs) at the Golgi and play a role, along with adaptor protein complex 1 (AP‐1), in the sorting of newly synthesized lysosomal hydrolases to the endolysosomal system. However, the relative importance of the two types of coat proteins in this process is still unclear. Here, we report that inactivation of all three GGA genes in HeLa cells decreased the sorting efficiency of cathepsin D from 97% to 73% relative to wild‐type, with marked redistribution of the cation‐independent MPR from peripheral punctae to the trans‐Golgi network. In comparison, GNPTAB^−/− HeLa cells with complete inactivation of the mannose 6‐phosphate pathway sorted only 20% of the cathepsin D. We conclude that the residual sorting of cathepsin D in the GGA triple‐knockout cells is mediated by AP‐1.

中文翻译：

---

HeLa 细胞中三个 GGA 基因的失活部分损害了溶酶体酶分选

高尔基体定位的、含有 γ 耳的 ADP 核糖基化因子结合蛋白（GGA 1、2 和 3）是多域蛋白，可与高尔基体上的甘露糖 6-磷酸受体 (MPR) 结合，并与接头一起发挥作用蛋白质复合物 1 (AP-1)，用于将新合成的溶酶体水解酶分选至内溶酶体系统。然而，这两种外壳蛋白在这一过程中的相对重要性仍不清楚。在这里，我们报告说，HeLa 细胞中所有三个GGA基因的失活使组织蛋白酶 D 的分选效率从 97% 降低到 73%，相对于野生型，阳离子非依赖性 MPR 从外周点显着重新分布到反式高尔基体。网络。相比之下，GNPTAB ^-/-甘露糖 6-磷酸途径完全失活的 HeLa 细胞仅分选了 20% 的组织蛋白酶 D。我们得出结论，GGA 三重敲除细胞中组织蛋白酶 D 的残余分选是由 AP-1 介导的。