Single, context-specific glycans can target misfolded glycoproteins for ER-associated degradation

Eric D. Spear, Davis T.W. Ng

Research output: Contribution to journalArticlepeer-review

Abstract

The endoplasmic reticulum (ER) maintains an environment essential for secretory protein folding. Consequently, the premature transport of polypeptides would be harmful to the cell. To avert this scenario, mechanisms collectively termed "ER quality control" prevent the transport of nascent polypeptides until they properly fold. Irreversibly misfolded molecules are sorted for disposal by the ER-associated degradation (ERAD) pathway. To better understand the relationship between quality control and ERAD, we studied a new misfolded variant of carboxypeptidase Y (CPY). The molecule was recognized and retained by ER quality control but failed to enter the ERAD pathway. Systematic analysis revealed that a single, specific N-linked glycan of CPY was required for sorting into the pathway. The determinant is dependent on the putative lectin-like receptor Htm1/Mnl1p. The discovery of a similar signal in misfolded proteinase A supported the generality of the mechanism. These studies show that specific signals embedded in glycoproteins can direct their degradation if they fail to fold.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalJournal of Cell Biology
Volume169
Issue number1
DOIs
StatePublished - Apr 11 2005
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Single, context-specific glycans can target misfolded glycoproteins for ER-associated degradation'. Together they form a unique fingerprint.

Cite this