COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation
COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation
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DOI：
10.1111/j.1600-0854.2005.00376.x
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发表时间：
2006-02-01
期刊：
影响因子：
4.5
通讯作者：
Lupashin, V
中科院分区：
文献类型：
--
作者：
Shestakova, A;Zolov, S;Lupashin, V
保守寡聚高尔基体（COG）复合体的缺陷导致蛋白质糖基化的多重缺陷。另一方面，Cog 3 p（COG 3 KD）的急性敲低（KD）引起高尔基体内COG复合物依赖性（CCD）囊泡的积累。在这里，我们分析了COG 3 KD不同阶段的细胞表型，以揭示COG功能和糖基化障碍之间的分子联系。这是第一次，我们证明了中间高尔基体酶被暂时重新定位到CCD囊泡在COG 3 KD细胞。因此，质膜（CD 44）和溶酶体（Lamp 2）糖蛋白的高尔基体修饰被扭曲。这些蛋白质的定位没有改变，表明顺向运输和准确分选不需要COG复合物。COG 7 KD和双COG 3/COG 7 KD引起类似的缺陷，高尔基体交通和糖基化，这表明整个COG复合物协调回收中间高尔基体驻留蛋白。COG复合物依赖对接的孤立的CCD囊泡在体外重建，支持其作为功能性贩运中间体的作用。总之，这些数据表明，不断循环的中间高尔基体酶的CCD囊泡从远端车厢运输。COG复合物功能障碍导致糖基转移酶与通过沿着分泌途径的顺行货物分子分离，从而影响正常的蛋白质糖基化。
Defects in conserved oligomeric Golgi (COG) complex result in multiple deficiencies in protein glycosylation. On the other hand, acute knock-down (KD) of Cog3p (COG3 KD) causes accumulation of intra-Golgi COG complex-dependent (CCD) vesicles. Here, we analyzed cellular phenotypes at different stages of COG3 KD to uncover the molecular link between COG function and glycosylation disorders. For the first time, we demonstrated that medial-Golgi enzymes are transiently relocated into CCD vesicles in COG3 KD cells. As a result, Golgi modifications of both plasma membrane (CD44) and lysosomal (Lamp2) glycoproteins are distorted. Localization of these proteins is not altered, indicating that the COG complex is not required for anterograde trafficking and accurate sorting. COG7 KD and double COG3/COG7 KD caused similar defects with respect to both Golgi traffic and glycosylation, suggesting that the entire COG complex orchestrates recycling of medial-Golgi-resident proteins. COG complex-dependent docking of isolated CCD vesicles was reconstituted in vitro, supporting their role as functional trafficking intermediates. Altogether, the data suggest that constantly cycling medial-Golgi enzymes are transported from distal compartments in CCD vesicles. Dysfunction of COG complex leads to separation of glycosyltransferases from anterograde cargo molecules passing along secretory pathway, thus affecting normal protein glycosylation.