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Originally published In Press as doi:10.1074/jbc.M608764200 on October 16, 2006

J. Biol. Chem., Vol. 281, Issue 50, 38343-38350, December 15, 2006
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Deletion of Core Fucosylation on {alpha}3beta1 Integrin Down-regulates Its Functions*

Yanyang Zhao{ddagger}, Satsuki Itoh§, Xiangchun Wang{ddagger}, Tomoya Isaji{ddagger}, Eiji Miyoshi{ddagger}, Yoshinobu Kariya||, Kaoru Miyazaki||, Nana Kawasaki§, Naoyuki Taniguchi{ddagger}**1, and Jianguo Gu{ddagger}2

From the {ddagger}Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, the §National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, the ||Division of Cell Biology, Kihara Institute of Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, the **Department of Disease Glycomics, Research Institute for Microbial Diseases, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, and the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsusima, Aobaku, Sendai, Miyagi 981-8558, Japan

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}3beta1 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}3beta1 integrin-mediated events has been studied by using Fut8+/+ and Fut8–/– embryonic fibroblasts, respectively. We found that the core fucosylation of {alpha}3beta1 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}3beta1 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}3beta1 integrin.


Received for publication, September 11, 2006 , and in revised form, October 13, 2006.

* This work was supported by Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, and the 21st Century COE program from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence may be addressed. Tel.: 81-6-879-4137; Fax: 81-6-879-4137; E-mail: tani52{at}wd5.so-net.ne.jp. 2 To whom correspondence may be addressed. Tel.: 81-22-727-0216; Fax: 81-22-727-0078; E-mail: jgu{at}tohoku-pharm.ac.jp.


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