Kim S, Miura Y, Etchison J R, Freeze H H
Korea Basic Science Institute, Taejon 305-333, South Korea.
Glycoconj J. 2001 Aug;18(8):623-33. doi: 10.1023/a:1020691619908.
We examined the functional co-localization and continuity of glycosyltransferases and sugar nucleotide transporters in the Golgi of two Chinese hamster ovary (CHO) cell lines that synthesize different types of O-linked oligosaccharides. CHO cells normally synthesize primarily Sia2,3Galbeta1,3GalNAc- on glycoproteins. CHO cells transfected with core-2 GlcNAc transferase (Core 2) can synthesize glycoproteins containing branched O-linked oligosaccharides with poly-N-acetyllactosamines. CHO lines incubated with [(3)H]galactose and GalNAc-alpha-phenyl (GAP) as a primer, synthesize labeled glycoside products that faithfully resemble those found on the endogenous acceptors: CHO cells make Sia2,3[(3)H]Gal(beta)1,3GAP, while CHO Core2 cells synthesize GAPs with complex branched chains including poly-N-acetyllactosamines. To determine if isolated Golgi preparations make similar products, we prepared Golgi by established homogenization methods, documented their intactness, and added tracer UDP-[(3)H]Gal, unlabeled sugar nucleotides, and GAP. CHO Golgi preparations synthesized only Sia2,3[(3)H]Gal(beta)1,3GAP. CHO Core2, also made this product and a small amount of Core-2 GlcNAc transferase-dependent products. No endogenous glycoproteins were labeled. However, when either cell line was gently permeabilized with streptolysin-O or given hypo-osmotic shock, both GAP and endogenous acceptors were efficiently glycosylated within an intact functional Golgi lumen and remained there. Significantly, Golgi from CHO Core2 cells made mostly branched GAP products including some with poly-N-acetyllactosamines as complex as those made and secreted by living cells incubated with GAP. These results suggest that the lumen of the Golgi apparatus is functionally continuous or interconnected. Once glycosides diffuse into the Golgi lumen, they have access to all the sugar nucleotide transporters and glycosyltransferases used for complex GAP-based products without requiring metabolic energy or inter-vesicular transport. Glycosylation of artificial acceptors could be used to track the functional continuity or co-localization of multiple glycosyltransferases and transporters under conditions where Golgi morphology disintegrates and/or reappears.
我们研究了两种合成不同类型O-连接寡糖的中国仓鼠卵巢(CHO)细胞系高尔基体中糖基转移酶和糖核苷酸转运体的功能共定位及连续性。CHO细胞通常主要在糖蛋白上合成Sia2,3Galβ1,3GalNAc-。用核心2 N-乙酰葡糖胺转移酶(Core 2)转染的CHO细胞能够合成含有带有多聚N-乙酰乳糖胺的分支O-连接寡糖的糖蛋白。用[³H]半乳糖和GalNAc-α-苯基(GAP)作为引物孵育的CHO细胞系,合成的标记糖苷产物与内源性受体上的产物如实地相似:CHO细胞产生Sia2,3[³H]Gal(β)1,3GAP,而CHO Core2细胞合成带有包括多聚N-乙酰乳糖胺的复杂分支链的GAP。为了确定分离的高尔基体制剂是否产生类似的产物,我们通过既定的匀浆方法制备高尔基体,记录其完整性,并加入示踪剂UDP-[³H]半乳糖、未标记的糖核苷酸和GAP。CHO高尔基体制剂仅合成Sia2,3[³H]Gal(β)1,3GAP。CHO Core2也产生了这种产物以及少量依赖于核心2 N-乙酰葡糖胺转移酶的产物。没有内源性糖蛋白被标记。然而,当用链球菌溶血素-O轻轻通透任一细胞系或给予低渗休克时,GAP和内源性受体在完整的功能性高尔基体腔内均被有效糖基化并保留在那里。值得注意的是,来自CHO Core2细胞的高尔基体产生的大多是分支GAP产物,包括一些带有与用GAP孵育的活细胞产生并分泌的产物一样复杂的多聚N-乙酰乳糖胺的产物。这些结果表明高尔基体腔在功能上是连续的或相互连接的。一旦糖苷扩散到高尔基体腔内,它们就能接触到用于基于GAP的复杂产物的所有糖核苷酸转运体和糖基转移酶,而无需代谢能量或囊泡间运输。在高尔基体形态解体和/或重新出现的条件下,人工受体的糖基化可用于追踪多种糖基转移酶和转运体的功能连续性或共定位。