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.
alpha1,6-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.
Lee
Seung Ho
SH
Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871.
Takahashi
Motoko
M
Honke
Koichi
K
Miyoshi
Eiji
E
Osumi
Daisuke
D
Sakiyama
Haruhiko
H
Ekuni
Atsuko
A
Wang
Xiangchun
X
Inoue
Shinya
S
Gu
Jianguo
J
Kadomatsu
Kenji
K
Taniguchi
Naoyuki
N
D000818:Animals; D005643:Fucose / Q000737:chemistry / Q000378:metabolism*; D005647:Fucosyltransferases / Q000172:deficiency / Q000235:genetics*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015854:Up-Regulation / Q000502:physiology
D018972:Insulin-Like Growth Factor Binding Protein 3; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase