title: Phenotype changes of Fut8 knockout mouse: core fucosylation is crucial for the function of growth factor receptor(s).
abstract: Alpha1,6-fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue to N-linked oligosaccharides on glycoproteins by means of an alpha1,6-linkage to form core fucosylation in mammals. In mice, disruption of Fut8 induces severe growth retardation, early death during postnatal development, and emphysema-like changes in the lung. A marked dysregulation of TGF-beta1 receptor activation and signaling in Fut8-null mice lung results in overexpression of matrix metalloproteinases (MMPs), such as MMP12 and MMP13, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, which contributes to the destructive emphysema-like phenotype observed in Fut8-null mice. Furthermore, therapeutic administration of exogenous TGF-beta1 rescued the null mice from the emphysema-like phenotype. On the other hand, absence of Fut8 on EGF or PDGF receptor results in down-regulation of the receptor-mediated signaling, which is a plausible factor that may be responsible for the growth retardation. Reintroduction of the Fut8 gene to Fut8-null cells potentially rescued these receptor-mediated signaling impaired in null cells. Collectively, these results suggest that core fucosylation is crucial for growth factor receptors such as TGF-beta1 and EGF receptor-mediated biological functions.
authors.affiliation: Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Wang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D017978:Receptors, Growth Factor / Q000378:metabolism / Q000502:physiology*
chemical_list: D017978:Receptors, Growth Factor; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase