Deletion of core fucosylation on α3β1 integrin down-regulates its functions
Deletion of core fucosylation on α3β1 integrin down-regulates its functions
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DOI：
10.1074/jbc.m608764200
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发表时间：
2006-12-15
影响因子：
4.8
通讯作者：
Gu, Jianguo
中科院分区：
文献类型：
--
作者：
Zhao, Yanyang;Itoh, Satsuki;Gu, Jianguo
糖蛋白的核心岩藻糖基化（α 1，6-岩藻糖基化）广泛分布于哺乳动物组织中。最近，通过对α 1，6-岩藻糖基转移酶（Fut 8）敲除小鼠的研究，进一步报道了α 1，6-岩藻糖基化是非常关键的，其显示了肺气肿样变化和严重生长迟缓的表型。在这项研究中，我们广泛研究了核心岩藻糖基化对α 3 β 1整合素的影响，并首次发现Fut 8对这种整合素的功能做出了重要贡献。已经分别使用Fut 8（+/+）和Fut 8（-/-）胚胎成纤维细胞研究了核心岩藻糖基化在α 3 β 1整联蛋白介导的事件中的作用。我们发现，α 3 β 1整合素（层粘连蛋白5的主要受体）的核心岩藻糖基化在Fut 8（+/+）细胞中丰富，但在Fut 8（-/-）细胞中完全消失，这与Fut 8（-/-）细胞中α 3 β 1整合素介导的迁移缺陷有关。此外，在Fut 8（-/-）细胞中整合素介导的细胞信号传导减少。Fut 8的重新引入可能恢复层粘连蛋白5诱导的迁移和细胞内信号传导。总的来说，这些结果表明核心岩藻糖基化对于α 3 β 1整联蛋白的功能是必不可少的。
The core fucosylation (alpha 1,6-fucosylation) of glycoprotein is widely distributed in mammalian tissues. Recently alpha 1,6-fucosylation has been further reported to be very crucial by the study of alpha 1,6-fucosyltransferase (Fut8)-knock-out mice, which shows the phenotype of emphysema-like changes in the lung and severe growth retardation. In this study, we extensively investigated the effect of core fucosylation on alpha 3 beta 1 integrin and found for the first time that Fut8 makes an important contribution to the functions of this integrin. The role of core fucosylation in alpha 3 beta 1 integrin-mediated events has been studied by using Fut8(+/+) and Fut8(-/-) embryonic fibroblasts, respectively. We found that the core fucosylation of alpha 3 beta 1 integrin, the major receptor for laminin 5, was abundant in Fut8(+/+) cells but was totally abolished in Fut8(-/-) cells, which was associated with the deficient migration mediated by alpha 3 beta 1 integrin in Fut8(-/-) cells. Moreover integrin-mediated cell signaling was reduced in Fut8(-/-) cells. The reintroduction of Fut8 potentially restored laminin 5-induced migration and intracellular signaling. Collectively, these results suggested that core fucosylation is essential for the functions of alpha 3 beta 1 integrin.