N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on alpha3beta1 integrin-mediated cell migration.
N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on alpha3beta1 integrin-mediated cell migration.
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发表时间：
2006
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通讯作者：
Yanyang Zhao;T. Nakagawa;S. Itoh;K. Inamori;T. Isaji;Y. Kariya;A. Kondo;E. Miyoshi;K. Miyazaki-K.-Miyaza
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作者：
Yanyang Zhao;T. Nakagawa;S. Itoh;K. Inamori;T. Isaji;Y. Kariya;A. Kondo;E. Miyoshi;K. Miyazaki-K.-Miyaza
N-乙酰氨基葡萄糖转移酶 V (GnT-V) 催化 N-聚糖的 β1,6-GlcNAc 分支的添加，从而有助于转移。 N-乙酰氨基葡萄糖转移酶 III (GnT-III) 催化 N-聚糖中平分 GlcNAc 结构的形成，从而抑制转移。长期以来，人们假设体内也存在GnT-III作用对GnT-V产物形成的抑制，从而导致GnT-V生物学功能的抑制。为了测试这一点，我们对分别转染了 GnT-III、GnT-V 或两者的 MKN45 细胞进行了比较。我们发现，在 GnT-V 转染子的情况下，α3β1 整合素介导的层粘连蛋白 5 上的细胞迁移大大增强。引入 GnT-III 后，这种增强的细胞迁移被显着阻断。一致地，在 GnT-III 和 GnT-V 的双转染子中观察到整联蛋白 α3 亚基上的平分 GlcNAc 增加，但 β1,6-GlcNAc 支链 N-聚糖减少。相反，在人神经母细胞瘤细胞系 CHP134 细胞中，GnT-III 敲低导致层粘连蛋白 5 上的迁移增加，同时 α3 亚基上的 β1,6-GlcNAc 分支 N 聚糖增加。因此，在本研究中，GnT-III优先修饰α3亚基可能可以解释为什么GnT-III抑制GnT-V诱导的细胞迁移。总而言之，我们的结果首次证明 GnT-III 和 GnT-V 可以竞争性修饰相同的靶糖蛋白，并进一步正向或负向调节其生物学功能。
N-acetylglucosaminyltransferase V (GnT-V) catalyzes the addition of beta1,6-GlcNAc branching of N-glycans, which contributes to metastasis. N-acetylglucosaminyltransferase III (GnT-III) catalyzes the formation of a bisecting GlcNAc structure in N-glycans, resulting in the suppression of metastasis. It has long been hypothesized that the suppression of GnT-V product formation by the action of GnT-III would also exist in vivo, which will consequently lead to the inhibition of biological functions of GnT-V. To test this, we draw a comparison among MKN45 cells, which were transfected with GnT-III, GnT-V, or both, respectively. We found that alpha3beta1 integrin-mediated cell migration on laminin 5 was greatly enhanced in the case of GnT-V transfectant. This enhanced cell migration was significantly blocked after the introduction of GnT-III. Consistently, an increase in bisected GlcNAc but a decrease in beta1,6-GlcNAc-branched N-glycans on integrin alpha3 subunit was observed in the double transfectants of GnT-III and GnT-V. Conversely, GnT-III knockdown resulted in increased migration on laminin 5, concomitant with an increase in beta1,6-GlcNAc-branched N-glycans on the alpha3 subunit in CHP134 cells, a human neuroblastoma cell line. Therefore, in this study, the priority of GnT-III for the modification of the alpha3 subunit may be an explanation for why GnT-III inhibits GnT-V-induced cell migration. Taken together, our results demonstrate for the first time that GnT-III and GnT-V can competitively modify the same target glycoprotein and furthermore positively or negatively regulate its biological functions.