β-Galactoside α2,6-Sialyltransferase I Cleavage by BACE1 Enhances the Sialylation of Soluble Glycoproteins: A NOVEL REGULATORY MECHANISM FOR α2,6-SIALYLATION

• Published in: The Journal of biological chemistry Vol. 282; no. 48; pp. 34896 - 34903
• Main Authors: Sugimoto, Ichiro, Futakawa, Satoshi, Oka, Ritsuko, Ogawa, Kazuko, Marth, Jamey D, Miyoshi, Eiji, Taniguchi, Naoyuki, Hashimoto, Yasuhiro, Kitazume, Shinobu
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 30.11.2007
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M704766200

BACE1 (β-site amyloid precursor protein-cleaving enzyme-1) is a membrane-bound aspartic protease that cleaves amyloid precursor protein to produce a neurotoxic peptide, amyloid β-peptide, and has been implicated in triggering the pathogenesis of Alzheimer disease. We showed previously that BACE1 cleaves β-galactoside α2,6-sialyltransferase I (ST6Gal I) to initiate its secretion, but it remained unclear how BACE1 affects the cellular level of α2,6-sialylation. Here, we found that BACE1 overexpression in Hep3B cells increased the sialylation of soluble secreted glycoproteins, but did not affect cell-surface sialylation. The sialylation of soluble glycoproteins was not increased by ST6Gal I overexpression alone, but was increased by co-overexpression of ST6Gal I and BACE1 or by expression of the soluble form of ST6Gal I, suggesting that soluble ST6Gal I produced by BACE1 plays, at least in part, a role in the sialylation of soluble glycoproteins. We also found that plasma glycoproteins from BACE1-deficient mice exhibited reduced levels of α2,6-sialylation compared with those from wild-type mice. We propose a novel regulatory mechanism in which cleavage and secretion of ST6Gal I enhance the sialylation of soluble glycoprotein substrates.