The Conserved Oligomeric Golgi (COG) complex is an eight subunit protein complex associated with Golgi membranes. Genetic defects affecting individual COG subunits cause congenital disorders of glycosylation (CDGs), due to mislocalization of Golgi proteins involved in glycosylation mechanisms. While the resulting defects in N-and O-glycosylation have been extensively studied, no corresponding study of proteoglycan (PG) synthesis has been undertaken. We here show that glycosaminoglycan (GAG) modification of PGs is significantly reduced, regardless which COG subunit that is missing in HEK293T cells. Least reduction was observed for cells lacking COG1 and COG8 subunits, that bridge the A and B lobes of the complex. Lack of these subunits did not reduce GAG chain lengths of secreted PGs, which was reduced in cells lacking any other subunit (COG2-7). COG3 knock out (KO) cells had particularly reduced ability to polymerize GAG chains. For cell-associated GAGs, the mutant cell lines, except COG4 and COG7 KO, displayed longer GAG chains than wild-type cells, indicating that COG subunits play a role in cellular turnover of PGs. In light of the important roles PGs play in animal development, the effects KO of individual COG subunits have on GAG synthesis could explain the variable severity of COG associated CDGs.

中文翻译：

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保守的寡聚高尔基亚基缺陷 HEK293T 细胞中的蛋白多糖合成受到不同的影响，这取决于缺乏的亚基

保守寡聚高尔基体 (COG) 复合物是与高尔基体膜相关的八个亚基蛋白质复合物。由于参与糖基化机制的高尔基体蛋白的错误定位，影响个体 COG 亚基的遗传缺陷会导致先天性糖基化 (CDG) 障碍。虽然已经广泛研究了 N-和 O-糖基化产生的缺陷，但尚未对蛋白多糖 (PG) 合成进行相应的研究。我们在这里表明，无论 HEK293T 细胞中缺少哪个 COG 亚基，PG 的糖胺聚糖 (GAG) 修饰都显着减少。对于缺乏 COG1 和 COG8 亚基的细胞观察到的减少最少，这些亚基连接了复合物的 A 和 B 叶。缺乏这些亚基并不会减少分泌型 PG 的 GAG 链长度，而在缺乏任何其他亚基 (COG2-7) 的细胞中，GAG 链长度会减少。COG3 敲除 (KO) 细胞聚合 GAG 链的能力特别低。对于细胞相关的 GAG，除了 COG4 和 COG7 KO 外，突变细胞系显示出比野生型细胞更长的 GAG 链，表明 COG 亚基在 PG 的细胞周转中发挥作用。鉴于 PG 在动物发育中的重要作用，个体 COG 亚基的 KO 对 GAG 合成的影响可以解释 COG 相关 CDG 的不同严重程度。