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Glycobiology Advance Access published online on February 20, 2003

Glycobiology, doi:10.1093/glycob/cwg048
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Submitted on September 11, 2002
Revised on January 8, 2003
Accepted on January 13, 2003

© 2003 Oxford University Press

ORIGINAL ARTICLES

{alpha}1,3-fucosyltransferase IX (Fut9) determines Lewis X expression in brain

Shoko Nishihara 1, Hiroko Iwasaki 2, Kazuyuki Nakajima 3, Akira Togayachi 2, Yuzuru Ikehara 4, Takashi Kudo 2, Yasunori Kushi 5, Akiko Furuya 6, Kenya Shitara 6, Hisashi Narimatsu 2*

1 Division of Cell Biology, Institute of Life Science, Soka University, Tangi-cho, Hachioji, Tokyo 192-8577
2 Division of Cell Biology, Institute of Life Science, Soka University, Tangi-cho, Hachioji, Tokyo 192-8577; Glycogene Function Team, Research Center for Glycoscience (RCG), National Institute of Advanced Industrial Science and Technology (AIST), Central-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568
3 Division of Neurochemistry, Institute of Life Science, Soka University, Tangi-cho, Hachioji, Tokyo 192-8577
4 Division of Oncological Pathology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-0021
5 Department of Medical Biochemistry, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8513
6 Cell Regulation Analysis Team, Research Center for Glycoscience (RCG), National Institute of Advanced Industrial Science and Technology (AIST), Central-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568; Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533, Japan

* To whom correspondence should be addressed. E-mail: h.narimatsu{at}aist.go.jp.

Abstract

The expression of the Lewis x (Lex) carbohydrate structure in brain is developmentally regulated, and considered to play a role in cell-cell interaction during neuronal development. Mice possess three functional {alpha}1,3-fucosyltransferase genes, Fut4, Fut7, and Fut9. Fut7 is known to have no activity to synthesize Lex. In the present study, the relative activities of Fut4 and Fut9 for Lex synthesis were determined using recombinant enzymes. Fut9 exhibited very strong activity for oligosaccharide acceptors and glycolipid acceptors, i.e. more than 10 and 100 fold, respectively, that of Fut4. Furthermore, both cerebrum and cerebellum at various stages of development (E17, P0, P7, P30, P100) expressed 15-100 times more Fut9 transcript than Fut4 transcript. Neurons and astrocytes in primary culture also expressed 10-15 times more Fut9 than Fut4 transcript. Moreover, {alpha}1,3-fucosyltransferase activity toward a polylactosamine chain in homogenates of brain tissues and primary cultured cells showed a pattern typical of Fut9, not Fut4. The developmental profile of activity for the synthesis of Lex was well correlated with that of Fut9 transcript. Immunohistochemistry with anti-Fut9 mAb revealed the distribution of the Lex structure. These results showed that Fut9 is the most responsible enzyme for the synthesis of Lex in brain.


{alpha}1,3-fucosyltransferase, Fut4, Fut9, Lewis x, SSEA-1
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