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Beta-galactoside alpha2,6-sialyltransferase I cleavage by BACE1 enhances the sialylation of soluble glycoproteins. A novel regulatory mechanism for alpha2,6-sialylation.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2007 Nov 30; Vol. 282 (48), pp. 34896-903. Date of Electronic Publication: 2007 Sep 26. - Publication Year :
- 2007
-
Abstract
- BACE1 (beta-site amyloid precursor protein-cleaving enzyme-1) is a membrane-bound aspartic protease that cleaves amyloid precursor protein to produce a neurotoxic peptide, amyloid beta-peptide, and has been implicated in triggering the pathogenesis of Alzheimer disease. We showed previously that BACE1 cleaves beta-galactoside alpha2,6-sialyltransferase I (ST6Gal I) to initiate its secretion, but it remained unclear how BACE1 affects the cellular level of alpha2,6-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 alpha2,6-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.
- Subjects :
- Amyloid Precursor Protein Secretases metabolism
Animals
COS Cells
Chlorocebus aethiops
Humans
Male
Mice
Models, Biological
Rats
Rats, Wistar
Sialyltransferases chemistry
beta-D-Galactoside alpha 2-6-Sialyltransferase
Amyloid Precursor Protein Secretases chemistry
Aspartic Acid Endopeptidases metabolism
Gene Expression Regulation, Enzymologic
Glycoproteins chemistry
Sialyltransferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 282
- Issue :
- 48
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17897958
- Full Text :
- https://doi.org/10.1074/jbc.M704766200