Endoplasmic Reticulum-associated Degradation of Mammalian Glycoproteins Involves Sugar Chain Trimming to Man6-5GlcNAc2

Zehavit Frenkel, Walter Gregory, Stuart Kornfeld, Gerardo Z. Lederkremer

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Endoplasmic reticulum-associated degradation of misfolded or misprocessed glycoproteins in mammalian cells is prevented by inhibitors of class I α-mannosidases implicating mannose trimming from the precursor oligosaccharide Glc3Man9GlcNAc2 as an essential step in this pathway. However, the extent of mannose removal has not been determined. We show here that glycoproteins subject to endoplasmic reticulum-associated degradation undergo reglucosylation, deglucosylation, and mannose trimming to yield Man6GlcNAc2 and Man 5GlcNAc2. These structures lack the mannose residue that is the acceptor of glucose transferred by UDP-Glc:glycoprotein glucosyltransferase. This could serve as a mechanism for removal of the glycoproteins from folding attempts catalyzed by cycles of reglucosylation and calnexin/calreticulin binding and result in targeting of these molecules for proteasomal degradation.

Original languageEnglish
Pages (from-to)34119-34124
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number36
DOIs
StatePublished - Sep 5 2003

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