© 2006 The Japanese Biochemical Society.
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Loss of Core Fucosylation of Low-Density Lipoprotein Receptor–Related Protein-1 Impairs Its Function, Leading to the Upregulation of Serum Levels of Insulin-Like Growth Factor–Binding Protein 3 in Fut8–/– Mice
1 Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871; 2 Department of Molecular Medicine, Kochi University Medical School, Kochi 783-8505; and 3 Department of Biochemistry, Nagoya University School of Medicine, Nagoya 466-8550
To whom correspondence should be addressed. Tel: +81-6-6879-3421, Fax: +81-6-6879-3429, E-mail: proftani{at}biochem.med.osaka-u.ac.jp
1,6-Fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue from GDP-fucose to the innermost N-acetylglucosamine residue of N-glycans. Here we report that the loss of core fucosylation impairs the function of low-density lipoprotein (LDL) receptor–related protein-1 (LRP-1), a multifunctional scavenger and signaling receptor, resulting in a reduction in the endocytosis of insulin like growth factor (IGF)–binding protein-3 (IGFBP-3) in the cells derived from Fut8-null (Fut8–/–) mice. The reduced endocytosis was restored by the re-introduction of Fut8. Serum levels of IGFBP-3 were markedly upregulated in Fut8–/– mice. These data clearly indicate that core fucosylation is crucial for the scavenging activity of LRP-1 in vivo.
* These authors contributed equally to this work.
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