Deletion of core fucosylation on alpha3beta1 integrin down-regulates its functions.
The core fucosylation (alpha1,6-fucosylation) of glycoprotein is widely distributed in mammalian tissues. Recently alpha1,6-fucosylation has been further reported to be very crucial by the study of alpha1,6-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 alpha3beta1 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 alpha3beta1 integrin-mediated events has been studied by using Fut8(+/+) and Fut8(-/-) embryonic fibroblasts, respectively. We found that the core fucosylation of alpha3beta1 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 alpha3beta1 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 alpha3beta1 integrin.
Zhao
Yanyang
Y
Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Itoh
Satsuki
S
Wang
Xiangchun
X
Isaji
Tomoya
T
Miyoshi
Eiji
E
Kariya
Yoshinobu
Y
Miyazaki
Kaoru
K
Kawasaki
Nana
N
Taniguchi
Naoyuki
N
Gu
Jianguo
J
D000818:Animals; D001483:Base Sequence; D002240:Carbohydrate Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D017931:DNA Primers; D015536:Down-Regulation; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D034741:RNA, Small Interfering
D017931:DNA Primers; D039201:Integrin alpha3beta1; D034741:RNA, Small Interfering; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase