Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts

Tsutomu Nakagawa, Naofumi Uozumi, Miyako Nakano, Yoko Mizuno-Horikawa, Noriko Okuyama, Tomohiko Taguchi, Jianguo Gu, Akihiro Kondo, Naoyuki Taniguchi, Eiji Miyoshi

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

Fucosylated α-fetoprotein (AFP) is a highly specific tumor marker for hepatocellular carcinoma (HCC). However, the molecular mechanism by which serum level of fucosylated AFP increases in patients with HCC remains largely unknown. Here, we report that the fucosylation of glycoproteins could be a possible signal for secretion into bile ducts in the liver. We compared oligosaccharide structures on glycoproteins in human bile with those in serum by several types of lectin blot analyses. Enhanced binding of biliary glycoproteins to lectins that recognize a fucose residue was observed over a wide range of molecular weights compared with serum glycoproteins. A structural analysis of oligosaccharides by two-dimensional mapping high performance liquid chromatography and matrix-assisted laser desorption ionization time-of flight mass spectrometry confirmed the increases in the fucosylation of biliary glycoproteins. Purification followed by structural analysis on α1-antitrypsin, α1-acid glycoprotein and haptoglobin, which are synthesized in the liver, showed higher fucosylation in bile than in serum. To find direct evidence for fucosylation and sorting signal into bile ducts, we used α1-6 fucosyltransferase (Fut8)-deficient mice because fucosylation of glycoproteins produced in mouse liver was mainly an α1-6 linkage. Interestingly, the levels of α1-antitrypsin and α1-acid glycoprotein were quite low in bile of Fut8-deficient mice as compared with wild-type mice. An immunohistochemical study showed dramatic changes in the localization of these glycoproteins in the liver of Fut8-deficient mice. Taken together, these results suggest that fucosylation is a possible signal for the secretion of glycoproteins into bile ducts in the liver. A disruption in this system might involve an increase in fucosylated AFP in the serum of patients with HCC.

Original languageEnglish
Pages (from-to)29797-29806
Number of pages10
JournalJournal of Biological Chemistry
Volume281
Issue number40
DOIs
Publication statusPublished - 2006 Oct 6

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts'. Together they form a unique fingerprint.

Cite this