title: Screening a series of sialyltransferases for possible BACE1 substrates.
abstract: Deposition of amyloid beta-peptide (Abeta) and neurofibrillary tangles in the brain are hallmarks of Alzheimer's disease (AD) pathogenesis. BACE1, a membrane-bound aspartic protease that cleaves amyloid precursor protein (APP) to produce Abeta, has been implicated in triggering the pathogenesis of the disease. We previously reported that BACE1 also cleaved alpha2,6-sialyltransferase (ST6Gal I) in the Golgi apparatus and induced its secretion from the cell. Since most glycosyltransferases show Golgi localization and many of these are cleaved and secreted from the cell, we hypothesized that other glycosyltransferases may also be BACE1 substrates. Here, we focused on a series of sialyltransferases as candidates for BACE1 substrates. We found that BACE1 cleaved polysialyltransferase ST8Sia IV (PST) in vitro. We further found that BACE1 overexpression in COS cells enhanced the secretion of ST3Gal I, II, III and IV, although these sialyltransferases were not cleaved by BACE1 in vitro. These results suggest that BACE1 expression affects glycosylation not only by directly cleaving glycosyltransferases but also by modifying the secretion of glycosyltransferases via some other mechanisms.
authors.affiliation: Glyco-chain Functions Laboratory, Supra-biomolecular System Group, Frontier Research System, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tachida
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Oka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Shou
authors.initials: S
authors.lastname: Takashima
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000502:physiology*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D006031:Glycosylation; D006801:Humans; D012799:Sialyltransferases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D012799:Sialyltransferases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human